Body dysmorphic disorder in patients with acne: treatment challenges

Body dysmorphic disorder (BDD) is defined as a constant preoccupation with one or more non-existent or slight defects or flaws in the physical appearance, often resulting in repetitive behaviours like mirror checking and camouflaging. The prevalence is around 2% in the general population with up to 10% in dermatology patients. The prevalence of BDD in patients with acne ranges between 9% and 15%. BDD is associated with considerable psychosocial deterioration, poor quality of life, and development of comorbid mental health disorders, including obsessive compulsive disorder, depression, social anxiety and alcohol or illicit drug use. Such patients suffer tremendously and are at high risk of suicide. The rate of suicidal ideation reaches 79.5%. Of this number, nearly 27.6% make failed suicidal attempts each year and 0.3% of these attempts are successful..

Transgene-free, virus-based gene silencing in plants by artificial microRNAs derived from minimal precursors

[EN] Artificial microRNAs (amiRNAs) are highly specific, 21-nucleotide (nt) small RNAs designed to silence target transcripts. In plants, their application as biotechnological tools for functional genomics or crop improvement is limited by the need of transgenically expressing long primary miRNA (pri-miRNA) precursors to produce the amiRNAs in vivo. Here, we analyzed the minimal structural and sequence requirements for producing effective amiRNAs from the widely used, 521-nt long AtMIR390a pri-miRNA from Arabidopsisthaliana. We functionally screened in Nicotiana benthamiana a large collection of constructs transiently expressing amiRNAs against endogenous genes and from artificially shortened MIR390-based precursors and concluded that highly effective and accurately processed amiRNAs can be produced from a chimeric precursor of only 89 nt. This minimal precursor was further validated in A. thaliana transgenic plants expressing amiRNAs against endogenous genes. Remarkably, minimal but not full-length precursors produce authentic amiRNAs and induce widespread gene silencing in N.benthamiana when expressed from an RNA virus, which can be applied into leaves by spraying infectious crude extracts. Our results reveal that the length of amiRNA precursors can be shortened without affecting silencing efficacy, and that viral vectors including minimal amiRNA precursors can be applied in a transgene-free manner to induce whole-plant gene silencing.[EN] Graphical AbstractMinisterio de Ciencia y Universidades (MCU, Spain); Agencia Estatal de Investigacion (AEI, Spain); Fondo Europeo de Desarrollo Regional (FEDER, European Union) [PID2021-122186OB-100 and RYC-2017-21648 to A.C., PID2020-114691RB-I00 to J.-A.D. and PRE2019088439 to A.E.C.]; Consejo Superior de Investigaciones Cientificas (CSIC, Spain) [JAEINT 20 01312 to T.M.G.]; European Commission [Erasmus + Grant Agreement 20201-DE01-KA103-005653 to A.P.]. Funding for open access charge: CSIC Consejo Superior de Investigaciones Cientificas [PID2021-122186OB-100].Cisneros, AE.; Martin-Garcia, T.; Primc, A.; Kuziuta, W.; Sanchez-Vicente, J.; Aragonés, V.; Daròs, J.... (2023). Transgene-free, virus-based gene silencing in plants by artificial microRNAs derived from minimal precursors. Nucleic Acids Research. 51(19):10719-10736. https://doi.org/10.1093/nar/gkad7471071910736511

Enhanced cortical neural stem cell identity through short SMAD and WNT inhibition in human cerebral organoids facilitates emergence of outer radial glial cells

Cerebral organoids exhibit broad regional heterogeneity accompanied by limited cortical cellular diversity despite the tremendous upsurge in derivation methods, suggesting inadequate patterning of early neural stem cells (NSCs). Here we show that a short and early Dual SMAD and WNT inhibition course is necessary and sufficient to establish robust and lasting cortical organoid NSC identity, efficiently suppressing non-cortical NSC fates, while other widely used methods are inconsistent in their cortical NSC-specification capacity. Accordingly, this method selectively enriches for outer radial glia NSCs, which cyto-architecturally demarcate well-defined outer sub-ventricular-like regions propagating from superiorly radially organized, apical cortical rosette NSCs. Finally, this method culminates in the emergence of molecularly distinct deep and upper cortical layer neurons, and reliably uncovers cortex-specific microcephaly defects. Thus, a short SMAD and WNT inhibition is critical for establishing a rich cortical cell repertoire that enables mirroring of fundamental molecular and cyto-architectural features of cortical development and meaningful disease modelling

Aged soils contribute little to contemporary carbon cycling downstream of thawing permafrost peatlands

Funder: Department for Business, Energy and Industrial Strategy, UK Government; Id: http://dx.doi.org/10.13039/100011693Abstract: Vast stores of millennial‐aged soil carbon (MSC) in permafrost peatlands risk leaching into the contemporary carbon cycle after thaw caused by climate warming or increased wildfire activity. Here we tracked the export and downstream fate of MSC from two peatland‐dominated catchments in subarctic Canada, one of which was recently affected by wildlife. We tested whether thermokarst bog expansion and deepening of seasonally thawed soils due to wildfire increased the contributions of MSC to downstream waters. Despite being available for lateral transport, MSC accounted for ≤6% of dissolved organic carbon (DOC) pools at catchment outlets. Assimilation of MSC into the aquatic food web could not explain its absence at the outlets. Using δ13C‐Δ14C‐δ15N‐δ2H measurements, we estimated only 7% of consumer biomass came from MSC by direct assimilation and algal recycling of heterotrophic respiration. Recent wildfire that caused seasonally thawed soils to reach twice as deep in one catchment did not change these results. In contrast to many other Arctic ecosystems undergoing climate warming, we suggest waterlogged peatlands will protect against downstream delivery and transformation of MSC after climate‐ and wildfire‐induced permafrost thaw

Education and Training of Future Nuclear Engineers at DIN: From Advanced Computer Codes to an Interactive Plant Simulator

ABSTRACT This paper summarizes the work being performed at the Department of Nuclear Engineering (www.din.upm.es) of the Universidad Politécnica de Madrid to improve the education and training of future Spanish nuclear engineers according to the Bologna rules. We present two main efforts introduced in our programme: i) the understanding of the current computational methodologies/codes starting from the nuclear data processing, then the lattice and core calculations codes, and finally the power plant simulators, ii) the development of practical teaching-learning experiences with an Interactive Graphical Simulator of a real nuclear power plant

Role of Mitochondrial Complex IV in Age-Dependent Obesity

Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion

Desarrollo y validación preliminar del instrumento HSQoL-24 para evaluar calidad de vida en pacientes con hidradenitis supurativa

Introducción y objetivos: La hidradenitis supurativa (HS) es una enfermedad inflamatoria crónica de la piel que influencia negativamente la calidad de vida. En la actualidad no existen escalas en español que la evalúen. El objetivo del presente estudio fue desarrollar y validar un cuestionario específico para evaluar la calidad de vida en pacientes con HS. Material y métodos: Se desarrolló un estudio multicéntrico en España entre 2016 y 2017 para elaborar un cuestionario. Para ello se consideró tanto el marco conceptual como el conocimiento de la situación del paciente mediante la revisión de la bibliografía, reuniones de profesionales de diferentes áreas y entrevistas con pacientes. El cuestionario resultante se pasó a un grupo de 30 pacientes con 30 ± 10 días de intervalo entre uno y otro. Resultados: El análisis de fiabilidad muestra una buena consistencia interna y reproductibilidad con puntuación alfa de Cronbach de 0, 920 (test) y 0, 917 (retest) y coeficiente de correlación intraclase con DLQI y Skindex-29 de 0, 698 IC 95% (0, 456-0, 844) y 0, 900 IC 95% (0, 801-0, 951) respectivamente. Se establecieron puntos de corte para su uso y se comprobó que el instrumento es sensible al cambio. Conclusiones: El cuestionario HSQoL-24 es la primera prueba autoadministrada específica para evaluar la calidad de vida en HS en español. Sencillo de usar y puntuar por los profesionales. Este estudio demuestra que el instrumento es fiable, válido y sensible al cambio, pendiente de realizar estudio confirmatorio con una muestra mayor con 100 pacientes con HS. Introduction and objectives: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin with a negative impact on quality of life. Up to now, there are no disease specific instruments in Spanish to assess quality of life in HS. The objective of this study was to develop and validate a questionnaire to evaluate the quality of life in patients with HS. Material and methods: A multicentre study was carried out in Spain between 2016 and 2017 to develop the questionnaire. Both the conceptual framework and understanding of the patient''s situation were considered through a review of the literature, consensus of professionals from different related health areas, and in-depth interviews with patients. The resulting questionnaire was passed to a group of 30 patients with 30±10 days of interval between both assessments. Results: The reliability analysis shows a good internal consistency and reproducibility with Cronbach''s alpha score of 0.920 (test) and 0.917 (retest) and intraclass correlation coefficient with DLQI and Skindex-29 of 0.698 IC 95% (0.456-0.844) and 0.900 IC 95% (0.801-0.951) respectively. Cut-off points were established for its use and the instrument was found to be sensitive to change. Conclusions: The HSQoL-24 is the first disease-specific self-administered instrument to assess quality of life in patients with HS in Spanish. It is user friendly, and easy to score. This study shows that the instrument is reliable, valid and sensitive to change, pending confirmatory study with a larger sample of 100 patients with HS