Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations : Overlap of TWNK-related recessive disorders

Altres ajuts: This research was supported with cofounding from the European Regional Development Fund (ERDF), "A way to make Europe") (to IdC); S2017/BMD‑3721‑RAREGENOMICS‑CM from the Consejería de Educación e Investigación de la Comunidad de Madrid (to MAMP).Background: Perrault syndrome is a rare autosomal recessive disorder that is characterized by the association of sensorineural hearing impairment and ovarian dysgenesis in females, whereas males have only hearing impairment. In some cases, patients present with a diversity of neurological signs. To date, mutations in six genes are known to cause Perrault syndrome, but they do not explain all clinically-diagnosed cases. In addition, the number of reported cases and the spectra of mutations are still small to establish conclusive genotype-phenotype correlations. Methods: Affected siblings from family SH19, who presented with features that were suggestive of Perrault syndrome, were subjected to audiological, neurological and gynecological examination. The genetic study included genotyping and haplotype analysis for microsatellite markers close to the genes involved in Perrault syndrome, whole-exome sequencing, and Sanger sequencing of the coding region of the TWNK gene. Results: Three siblings from family SH19 shared similar clinical features: childhood-onset bilateral sensorineural hearing impairment, which progressed to profound deafness in the second decade of life; neurological signs (spinocerebellar ataxia, polyneuropathy), with onset in the fourth decade of life in the two females and at age 20 years in the male; gonadal dysfunction with early cessation of menses in the two females. The genetic study revealed two compound heterozygous pathogenic mutations in the TWNK gene in the three affected subjects: c.85C>T (p.Arg29∗), previously reported in a case of hepatocerebral syndrome; and a novel missense mutation, c.1886C>T (p.Ser629Phe). Mutations segregated in the family according to an autosomal recessive inheritance pattern. Conclusions: Our results further illustrate the utility of genetic testing as a tool to confirm a tentative clinical diagnosis of Perrault syndrome. Studies on genotype-phenotype correlation from the hitherto reported cases indicate that patients with Perrault syndrome caused by TWNK mutations will manifest neurological signs in adulthood. Molecular and clinical characterization of novel cases of recessive disorders caused by TWNK mutations is strongly needed to get further insight into the genotype-phenotype correlations of a phenotypic continuum encompassing Perrault syndrome, infantile-onset spinocerebellar ataxia, and hepatocerebral syndrome

New spinocerebellar ataxia subtype caused by SAMD9L mutation triggering mitochondrial dysregulation (SCA49)

Spinocerebellar ataxias consist of a highly heterogeneous group of inherited movement disorders clinically characterized by progressive cerebellar ataxia variably associated with additional distinctive clinical signs. The genetic heterogeneity is evidenced by the myriad of associated genes and underlying genetic defects identified. In this study, we describe a new spinocerebellar ataxia subtype in nine members of a Spanish five-generation family from Menorca with affected individuals variably presenting with ataxia, nystagmus, dysarthria, polyneuropathy, pyramidal signs, cerebellar atrophy and distinctive cerebral demyelination. Affected individuals presented with horizontal and vertical gaze-evoked nystagmus and hyperreflexia as initial clinical signs, and a variable age of onset ranging from 12 to 60 years. Neurophysiological studies showed moderate axonal sensory polyneuropathy with altered sympathetic skin response predominantly in the lower limbs. We identified the c.1877C > T (p.Ser626Leu) pathogenic variant within the SAMD9L gene as the disease causative genetic defect with a significant log-odds score (Z(max) = 3.43; theta = 0.00; P < 3.53 x 10(-5)). We demonstrate the mitochondrial location of human SAMD9L protein, and its decreased levels in patients' fibroblasts in addition to mitochondrial perturbations. Furthermore, mutant SAMD9L in zebrafish impaired mobility and vestibular/sensory functions. This study describes a novel spinocerebellar ataxia subtype caused by SAMD9L mutation, SCA49, which triggers mitochondrial alterations pointing to a role of SAMD9L in neurological motor and sensory functions. Corral-Juan et al. describe a novel dominantly inherited spinocerebellar ataxia subtype, SCA49, caused by SAMD9L mutation characterized by polyneuropathy, distinctive cerebral demyelination with gaze-evoked nystagmus and hyperreflexia as initial clinical signs. The study demonstrates the mitochondrial location of human SAMD9L protein triggering mitochondrial and lysosomal alterations

Large wood debris that clogged bridges followed by a sudden release: the 2019 flash flood in Catalonia

The aim is the reconstruction of the October 2019 flash flood, that was documented through extensive field work: rainfall (300 mm in just a few hours), flood marks, times of flood passage and witnesses' snapshots and reports, channel changes, log drift (20,000 trees) and woody debris at bridges, as well as large damage and six fatalities. The methods are: hydrological model built for the rainfall-runoff in the basin and the flood routing in the river, use of hydraulic principles such as flow at waterfalls, flow against obstacles (trees), etc. and finally 1D/2D free surface numerical models. The uppermost 100 km2 produced discharges of 700 m3/s (up to 50 m3/s/km2, locally). Three bridges failed, but their cascading failure (when one failure triggers the next one downstream) was not proved. The main channel widened more than 10 times, dragging away soil and vegetation like a bulldozer. The resulting large wood debris that clogged two bridges worsened the inundation. An anomalous flow downstream, probably a surge of around 1090 m3/s, due to the failure of a woody jam at a narrow bridge, took two lives. Water Authority is now warning flood planners that vegetated, torrential basins may cause catastrophic floods in the valley towns, if their narrow bridges are sensitive to woody debris.Catalan Water Authority and its Tarragona officers, Meteoprades and Fons Signatus, Joan March and a number of witnesses. The UPC's contribution was funded by the contract CTN2000029 of the “Agència Catalana de l′Aigua”. The UB's contribution has been developed within the framework of the AGORA project, funded by the "Agència Catalana de l′Aigua". Our thanks to the "Museu de la Vida Rural", in l′Espluga de Francolí, and all the citizens who contributed to the return of experience. The UIB's research has been supported by the Ministerio de Ciencia, Innovación y Universidades (CGL2017-82868-R and PID2020-113036RB-I00/AEI/10.13039/501100011033 research projects, which are partially supported by the European Regional Development Funds).Peer ReviewedPostprint (published version

Desenvolupament transversal de la competència informacional al segon semestre del Grau de Psicologia.

Podeu consultar la Vuitena trobada de professorat de Ciències de la Salut completa a: http://hdl.handle.net/2445/66524Buscar, seleccionar i gestionar informació especialitzada de manera estratègica, fent ús de diferents tecnologies i fonts d'informació és una de les competències transversals de la UB. Cinc assignatures del segon semestre de Psicologia van elaborar un pla d’actuació per treballar-la coordinadament. Els estudiants que van seguir aquesta formació van obtenir notables resultats quan s'enfrontaven a exercicis pràctics específics (identificació de paraules clau o factors d'impacte), però van mostrar mancances a l’hora de resoldre tasques que requerien la cerca avançada, l’ús de l'estil APA, la identificació de títols de revistes científiques o el coneixement global dels usos i recursos d'informació. No obstant, els estudiants que van rebre la formació van ser lleugerament més competents que els seus companys de darrer curs del grau (que no havien rebut aquesta formació coordinada, però que se'ls hi suposa experiència en cerca documental, atesa les demandes de les diferents assignatures que han cursat). D’altra banda, l'avaluació de la competència informacional no va resultar independent de la resta de competències avaluades ja que va correlacionar positivament, tant en la tasca de defensa oral, com en la puntuació de l'examen final de continguts bàsics de l'assignatura (valors rxy entre 0,09 i 0,18).Buscar, seleccionar i gestionar informació especialitzada de manera estratègica, fent ús de diferents tecnologies i fonts d'informació és una de les competències transversals de la UB. Cinc assignatures del segon semestre de Psicologia van elaborar un pla d’actuació per treballar-la coordinadament. Els estudiants que van seguir aquesta formació van obtenir notables resultats quan s'enfrontaven a exercicis pràctics específics (identificació de paraules clau o factors d'impacte), però van mostrar mancances a l’hora de resoldre tasques que requerien la cerca avançada, l’ús de l'estil APA, la identificació de títols de revistes científiques o el coneixement global dels usos i recursos d'informació. No obstant, els estudiants que van rebre la formació van ser lleugerament més competents que els seus companys de darrer curs del grau (que no havien rebut aquesta formació coordinada, però que se'ls hi suposa experiència en cerca documental, atesa les demandes de les diferents assignatures que han cursat). D’altra banda, l'avaluació de la competència informacional no va resultar independent de la resta de competències avaluades ja que va correlacionar positivament, tant en la tasca de defensa oral, com en la puntuació de l'examen final de continguts bàsics de l'assignatura (valors rxy entre 0,09 i 0,18)

1000 preguntes per 3 qüestionaris i 500 estudiants

Assignatura de Psicofisiologia, 2n semestre, Grau de Psicologia UB. 2013-2014Cada mes, els estudiants han de contestar un qüestionari amb preguntes relacionades amb els temes treballats fins el moment en l’assignatura. Respondre’l requereix la cerca informació específica en webs, llibres o articles científics. Disposen d’una setmana per contestar-lo, sense límit d’entrades

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

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Co-limitation towards lower latitudes shapes global forest diversity gradients

The latitudinal diversity gradient (LDG) is one of the most recognized global patterns of species richness exhibited across a wide range of taxa. Numerous hypotheses have been proposed in the past two centuries to explain LDG, but rigorous tests of the drivers of LDGs have been limited by a lack of high-quality global species richness data. Here we produce a high-resolution (0.025° × 0.025°) map of local tree species richness using a global forest inventory database with individual tree information and local biophysical characteristics from ~1.3 million sample plots. We then quantify drivers of local tree species richness patterns across latitudes. Generally, annual mean temperature was a dominant predictor of tree species richness, which is most consistent with the metabolic theory of biodiversity (MTB). However, MTB underestimated LDG in the tropics, where high species richness was also moderated by topographic, soil and anthropogenic factors operating at local scales. Given that local landscape variables operate synergistically with bioclimatic factors in shaping the global LDG pattern, we suggest that MTB be extended to account for co-limitation by subordinate drivers

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