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1.
Blood Cancer J ; 14(1): 75, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697976

RESUMEN

Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.


Asunto(s)
Galectinas , Ganglios Linfáticos , Linfoma Folicular , Microambiente Tumoral , Humanos , Linfoma Folicular/inmunología , Linfoma Folicular/patología , Linfoma Folicular/terapia , Ganglios Linfáticos/patología , Ganglios Linfáticos/inmunología , Microambiente Tumoral/inmunología , Esferoides Celulares , Inmunoterapia/métodos , Transducción de Señal , Células Tumorales Cultivadas
2.
Res Sq ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38746362

RESUMEN

Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes. However, environmental sensitivity genetic variants have proven challenging to detect. GWAS of monozygotic twin differences is a family-based variance analysis method, which is more robust to systemic biases that impact population-based methods. We combined data from up to 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct the largest GWAS meta-analysis of monozygotic phenotypic differences in children and adolescents/adults for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder (ADHD) symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism, and wellbeing. The SNP-heritability of variance in these phenotypes were estimated (h2: 0% to 18%), but were imprecise. We identified a total of 13 genome-wide significant associations (SNP, gene, and gene-set), including genes related to stress-reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. Monozygotic twins are an important new source of evidence about the genetics of environmental sensitivity.

3.
Lupus ; : 9612033241247103, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709545

RESUMEN

Cytomegalovirus (CMV) infection and disease is a condition usually described in immunocompromised patients, but among them, those with connective tissue diseases are poorly represented. Here we present the clinical, laboratory characteristics, management and outcomes of systemic lupus erythematosus (SLE) patients who presented with a CMV infection/disease to a high complexity hospital in southwestern Colombia between 2011 and 2020. 16 SLE patients were found to have a CMV infection. SLE was predominantly characterized by renal involvement (10 patients; 62.50%), and 14 patients (87.5%) were receiving steroids previous to the CMV infection. The entire sample required hospital admission, mainly related to acute kidney injury, and nine patients were admitted to the intensive care unit (ICU). Gastrointestinal organ damage was the most common CMV disease manifestation. All patients received ganciclovir, five of them (31.25%) suffered from septic shock, and seven (43.75%) died. Age ≥38 years and the presence of septic shock at admission were correlated to the mortality outcome. To our knowledge, this is the first publication evaluating SLE patients with CMV infection/disease in a Colombian population.

4.
J Reprod Infant Psychol ; : 1-12, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38482811

RESUMEN

AIMS/BACKGROUND: Assessing the intensity of perinatal grief is very important for identifying the more complex cases in mothers and fathers. Despite this, there are few assessment tools available. The aim of this study was to analyse the psychometric properties (factorial structure, reliability, and validity) of the Spanish version of the Perinatal Grief Intensity Scale (PGIS). DESIGN/METHODS: An online survey was completed by 291 mothers and fathers who had suffered perinatal loss in the previous six years. RESULTS: The results showed adequate fit indexes for the three-factor model of the PGIS: reality, confront others, and congruence. Reliability values for the overall scale and subscales were adequate. Finally, with regard to validity, significant (p < .05) and positive relationships were found with levels of complicated grief, event centrality, guilt, anxiety, and depression. There were also differences depending on whether participants exhibited high or low levels of complicated grief, and on the number of weeks of pregnancy at the time of the loss. CONCLUSION: In conclusion, the Spanish adaptation of the PGIS has adequate reliability and validity scores and a factorial structure consistent with the original version.

5.
Res Sq ; 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38405932

RESUMEN

Post-pregnancy breast cancer often carries a poor prognosis, posing a major clinical challenge. The increasing trend of later-life pregnancies exacerbates this risk, highlighting the need for effective chemoprevention strategies. Current options, limited to selective estrogen receptor modulators, aromatase inhibitors, or surgical procedures, offer limited efficacy and considerable side effects. Here, we report that cabergoline, a dopaminergic agonist, reduces the risk of breast cancer post-pregnancy in a Brca1/P53-deficient mouse model, with implications for human breast cancer prevention. We show that a single dose of cabergoline administered post-pregnancy significantly delayed the onset and reduced the incidence of breast cancer in Brca1/P53-deficient mice. Histological analysis revealed a notable acceleration in post-lactational involution over the short term, characterized by increased apoptosis and altered gene expression related to ion transport. Over the long term, histological changes in the mammary gland included a reduction in the ductal component, decreased epithelial proliferation, and a lower presence of recombinant Brca1/P53 target cells, which are precursors of tumors. These changes serve as indicators of reduced breast cancer susceptibility. Additionally, RNA sequencing identified gene expression alterations associated with decreased proliferation and mammary gland branching. Our findings highlight a mechanism wherein cabergoline enhances the protective effect of pregnancy against breast cancer by potentiating postlactational involution. Notably, a retrospective cohort study in women demonstrated a markedly lower incidence of post-pregnancy breast cancer in those treated with cabergoline compared to a control group. Our work underscores the importance of enhancing postlactational involution as a strategy for breast cancer prevention, and identifies cabergoline as a promising, low-risk option in breast cancer chemoprevention. This strategy has the potential to revolutionize breast cancer prevention approaches, particularly for women at increased risk due to genetic factors or delayed childbirth, and has wider implications beyond hereditary breast cancer cases.

6.
J Child Psychol Psychiatry ; 65(3): 308-315, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37792459

RESUMEN

BACKGROUND: Stress is a universal phenomenon and one of the most common precipitants of insomnia. However, not everyone develops insomnia after experiencing a stressful life event. This study aims to test aspects of Spielman's '3P model of insomnia' (during adolescence) by exploring the extent to which: (a) insomnia symptoms are predicted by polygenic scores (PGS); (b) life events predict insomnia symptoms; (c) the interaction between PGS and life events contribute to the prediction of insomnia symptoms; (d) gene-environment interaction effects remain after controlling for sex. METHODS: The sample comprised 4,629 twins aged 16 from the Twin Early Development Study who reported on their insomnia symptoms and life events. PGS for insomnia were calculated. In order to test the main hypothesis of this study (a significant interaction between PGS and negative life events), we fitted a series of mixed effect regressions. RESULTS: The best fit was provided by the model including sex, PGS for insomnia, negative life events, and their interactions (AIC = 26,158.7). Our results show that the association between insomnia symptoms and negative life events is stronger for those with a higher genetic risk for insomnia. CONCLUSIONS: This work sheds light on the complex relationship between genetic and environmental factors implicated for insomnia. This study has tested for the first time the interaction between genetic predisposition (PGS) for insomnia and environmental stressors (negative life events) in adolescents. This work represents a direct test of components of Spielman's 3P model for insomnia which is supported by our results.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Adolescente , Trastornos del Inicio y del Mantenimiento del Sueño/genética , Gemelos/genética , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Factores de Riesgo
7.
Pediatr Surg Int ; 40(1): 18, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38082019

RESUMEN

PURPOSE: The objective of this study was to determine the association between the presence of a microorganism resistant to the antibiotic used in empirical therapy and the development of intra-abdominal abscesses in children with perforated appendicitis. METHODS: A prospective cohort study was conducted in patients under 18 years of age who underwent laparoscopic appendectomy between November 1, 2019, and September 30, 2020, in whom perforated appendicitis was documented intraoperatively. Peritoneal fluid samples were taken for bacteria culture purposes, and clinical and microbiological data were collected from all patients. RESULTS: A total of 232 patients were included in the study. The most isolated microorganisms were Escherichia coli (80.14%) and Pseudomonas aeruginosa (7.45%). In addition, 5.31% of E. coli isolates were classified as ESBL-producing organisms. No association was found between a germ resistant to empiric antimicrobial therapy and the development of a postoperative intra-abdominal abscess. Multivariate analysis showed that being a high-risk patient on admission (OR 2.89 (p = 0.01)) was associated with the development of intra-abdominal abscesses postoperatively. CONCLUSION: E. coli was the most commonly isolated microorganism, with a low rate of ESBL-producing isolates. No association between resistance and risk of postoperative intra-abdominal abscess was found. However, it was identified that being a high-risk patient on admission was associated with this complication. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level I.


Asunto(s)
Absceso Abdominal , Apendicitis , Niño , Humanos , Adolescente , Estudios de Cohortes , Escherichia coli , Estudios Prospectivos , Apendicitis/complicaciones , Apendicitis/cirugía , Apendicitis/tratamiento farmacológico , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Complicaciones Posoperatorias/tratamiento farmacológico , Absceso Abdominal/tratamiento farmacológico , Apendicectomía/efectos adversos
8.
J Immunother Cancer ; 11(10)2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37899130

RESUMEN

BACKGROUND: Follicular lymphoma (FL), the most common indolent non-Hodgkin's Lymphoma, is a heterogeneous disease and a paradigm of the contribution of immune tumor microenvironment to disease onset, progression, and therapy resistance. Patient-derived models are scarce and fail to reproduce immune phenotypes and therapeutic responses. METHODS: To capture disease heterogeneity and microenvironment cues, we developed a patient-derived lymphoma spheroid (FL-PDLS) model culturing FL cells from lymph nodes (LN) with an optimized cytokine cocktail that mimics LN stimuli and maintains tumor cell viability. RESULTS: FL-PDLS, mainly composed of tumor B cells (60% on average) and autologous T cells (13% CD4 and 3% CD8 on average, respectively), rapidly organizes into patient-specific three-dimensional (3D) structures of three different morphotypes according to 3D imaging analysis. RNAseq analysis indicates that FL-PDLS reproduces FL hallmarks with the overexpression of cell cycle, BCR, or mTOR signaling related gene sets. FL-PDLS also recapitulates the exhausted immune phenotype typical of FL-LN, including expression of BTLA, TIGIT, PD-1, TIM-3, CD39 and CD73 on CD3+ T cells. These features render FL-PDLS an amenable system for immunotherapy testing. With this aim, we demonstrate that the combination of obinutuzumab (anti-CD20) and nivolumab (anti-PD1) reduces tumor load in a significant proportion of FL-PDLS. Interestingly, B cell depletion inversely correlates with the percentage of CD8+ cells positive for PD-1 and TIM-3. CONCLUSIONS: In summary, FL-PDLS is a robust patient-derived 3D system that can be used as a tool to mimic FL pathology and to test novel immunotherapeutic approaches in a context of personalized medicine.


Asunto(s)
Linfoma Folicular , Humanos , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/genética , Receptor 2 Celular del Virus de la Hepatitis A , Receptor de Muerte Celular Programada 1/metabolismo , Microambiente Tumoral , Medicina de Precisión
9.
JCPP Adv ; 3(2): e12167, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37753157

RESUMEN

Background: Insomnia with short sleep duration has been postulated as more severe than that accompanied by normal/long sleep length. While the short duration subtype is considered to have greater genetic influence than the other subtype, no studies have addressed this question. This study aimed to compare these subtypes in terms of: (1) the heritability of insomnia symptoms; (2) polygenic scores (PGS) for insomnia symptoms and sleep duration; (3) the associations between insomnia symptoms and a wide variety of traits/disorders. Methods: The sample comprised 4000 pairs of twins aged 16 from the Twins Early Development Study. Twin models were fitted to estimate the heritability of insomnia in both groups. PGS were calculated for self-reported insomnia and sleep duration and compared among participants with short and normal/long sleep duration. Results: Heritability was not significantly different in the short sleep duration group (A = 0.13 [95%CI = 0.01, 0.32]) and the normal/long sleep duration group (A = 0.35 [95%CI = 0.29, 0.40]). Shared environmental factors accounted for a substantial proportion of the variance in the short sleep duration group (C = 0.19 [95%CI = 0.05, 0.32]) but not in the normal/long sleep duration group (C = 0.00 [95%CI = 0.00, 0.04]). PGS did not differ significantly between groups although results were in the direction expected by the theory. Our results also showed that insomnia with short (as compared to normal/long) sleep duration had a stronger association with anxiety and depression (p < .05)-although not once adjusting for multiple testing. Conclusions: We found mixed results in relation to the expected differences between the insomnia subtypes in adolescents. Future research needs to further establish cut-offs for 'short' sleep at different developmental stages and employ objective measures of sleep.

10.
Nutrients ; 15(12)2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37375661

RESUMEN

The World Health Organization estimates that one fifth of university students have experienced major depressive disorder at some point in their lives. Nutrition may be one of the modifiable factors that influence the development of depression. Specifically, low omega-3 fatty acid and vitamin D levels, both nutrients found in high quantities in fish, have been linked to depressive disorders. The main objective of this study was to evaluate the prevalence of depression among young Spanish university students, in addition to the pattern of fish consumption among students and the possible relationship between fish consumption and the presence of depression. Data were collected retrospectively from a nationally representative sample of 11,485 Spanish university students aged 18 years or older in 11 Spanish universities, from 2012 to 2022. The respondents were analyzed according to frequency of consumption and compliance with weekly recommendations for fish intake and the presence of depression. Regression models were also performed to determine students' odds of depression as a function of compliance with recommendations according to selected sociodemographic variables. The prevalence of depression was 10.5%; it was more prevalent in women, older students and in those with both high and low BMIs. In addition, it was also more prevalent in those that lived outside the family home, with roommates and those who were employed. Sixty-seven percent of the students met the fish intake recommendations. The most common frequency of fish consumption was 1-2 times/week (44.2%), and the least frequent was 2.3% daily fish consumption. Students from northern universities were more likely to consume fish (68.4%) than those from southern universities (66.4%). Non-consumption of fish was found to increase the risk of depression (ORa = 1.45 (1.28-1.64); AF = 31.0% (21.9-39.0)), but it was the student's own conditions that had the greatest influence on the development of the disorder. In summary, a lower consumption of fish seems to be associated with a higher incidence of depression in Spanish university students; however, other social factors of the student may influence the development of the disorder, and all of this should be taken into account for the development of prevention strategies.


Asunto(s)
Depresión , Trastorno Depresivo Mayor , Animales , Femenino , Humanos , Depresión/epidemiología , Trastorno Depresivo Mayor/epidemiología , Prevalencia , Universidades , Estudios Retrospectivos , Encuestas y Cuestionarios , Estudiantes
11.
Br J Psychol ; 114(4): 797-818, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37070349

RESUMEN

Night-time is a period of great significance for many people who report paranormal experiences. However, there is limited understanding of the associations between sleep variables and seemingly paranormal experiences and/or beliefs. The aim of this review is to improve our understanding of these associations while unifying a currently fragmented literature-base into a structured, practical review. In this pre-registered scoping review, we searched for relevant studies in MEDLINE (PubMed), PsycINFO (EBSCO), Web of Science and EMBASE using terms related to sleep and ostensibly paranormal experiences and beliefs. Forty-four studies met all inclusion criteria. All were cross-sectional and most investigated sleep paralysis and/or lucid dreaming in relation to ostensibly paranormal experiences and paranormal beliefs. Overall, there were positive associations between many sleep variables (including sleep paralysis, lucid dreams, nightmares, and hypnagogic hallucinations) and ostensibly paranormal experiences and paranormal beliefs (including those of ghosts, spirits, and near-death experiences). The findings of this review have potential clinical implications such as reducing misdiagnosis and treatment development and provide foundations for further research. Our findings also highlight the importance of understanding why so many people report 'things that go bump in the night'.


Asunto(s)
Parálisis del Sueño , Humanos , Sueño , Alucinaciones
12.
Sleep ; 46(6)2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37106487

RESUMEN

STUDY OBJECTIVES: Digital technology use is associated with poor sleep quality in adolescence and young adulthood although research findings have been mixed. No studies have addressed the association between the two using a genetically informative twin design which could extend our understanding of the etiology of this relationship. This study aimed to test: (1) the association between adolescents' perceived problematic use of digital technology and poor sleep quality, (2) whether the association between problematic use of technology and poor sleep quality remains after controlling for familial factors, and (3) genetic and environmental influences on the association between problematic use of technology and poor sleep quality. METHODS: Participants were 2232 study members (18-year-old twins) of the Environmental Risk (E-Risk) Longitudinal Twin Study. The sample was 48.9% male, 90% white, and 55.6% monozygotic. We conducted regression and twin difference analyses and fitted twin models. RESULTS: Twin differences for problematic use of technology were associated with differences for poor sleep quality in the whole sample (p < 0.001; B = 0.15) and also when we limited the analyses to identical twins only (p < 0.001; B = 0.21). We observed a substantial genetic correlation between problematic use of technology and sleep quality (rA = 0.31), whereas the environmental correlation was lower (rE = 0.16). CONCLUSIONS: Adolescent reported problematic use of digital technology is associated with poor sleep quality-even after controlling for familial factors including genetic confounds. Our results suggest that the association between adolescents' sleep and problematic digital technology use is not accounted for by shared genetic liability or familial factors but could reflect a causal association. This robust association needs to be examined in future research designed to test causal associations.


Asunto(s)
Calidad del Sueño , Gemelos Monocigóticos , Adolescente , Humanos , Masculino , Adulto Joven , Adulto , Femenino , Gemelos Monocigóticos/genética , Sueño/genética , Estudios Longitudinales , Tecnología
13.
Leukemia ; 37(6): 1311-1323, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37031299

RESUMEN

Mantle cell lymphoma (MCL), a rare and aggressive B-cell non-Hodgkin lymphoma, mainly develops in the lymph node (LN) and creates a protective and immunosuppressive niche that facilitates tumor survival, proliferation and chemoresistance. To capture disease heterogeneity and tumor microenvironment (TME) cues, we have developed the first patient-derived MCL spheroids (MCL-PDLS) that recapitulate tumor oncogenic pathways and immune microenvironment in a multiplexed system that allows easy drug screening, including immunotherapies. MCL spheroids, integrated by tumor B cells, monocytes and autologous T-cells self-organize in disc-shaped structures, where B and T-cells maintain viability and proliferate, and monocytes differentiate into M2-like macrophages. RNA-seq analysis demonstrated that tumor cells recapitulate hallmarks of MCL-LN (proliferation, NF-kB and BCR), with T cells exhibiting an exhaustion profile (PD1, TIM-3 and TIGIT). MCL-PDLS reproduces in vivo responses to ibrutinib and demonstrates that combination of ibrutinib with nivolumab (anti-PD1) may be effective in ibrutinib-resistant cases by engaging an immune response with increased interferon gamma and granzyme B release. In conclusion, MCL-PDLS recapitulates specific MCL-LN features and in vivo responses to ibrutinib, representing a robust tool to study MCL interaction with the immune TME and to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.


Asunto(s)
Linfoma de Células del Manto , Humanos , Adulto , Línea Celular Tumoral , Linfoma de Células del Manto/patología , Resistencia a Antineoplásicos , Adenina/uso terapéutico , Microambiente Tumoral
14.
Agric Food Econ ; 11(1): 6, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36919115

RESUMEN

This study focuses on analysing the economic impact (in value-added terms) generated by Spanish wine exports during the period 2018-2020, characterized by significant geopolitical changes and market shocks produced by Brexit, the entry into force of the Federal Law on Viticulture and Winemaking in the Russian Federation, the imposition of tariffs by the USA and the COVID-19 pandemic. For this purpose, the multiregional input-output model was used to identify the overall effects (direct and indirect) in different countries deriving from the changes in final demand. The paper shows that both the world wine trade and Spanish wine exports have been negatively affected by the recent changes in the analysed period. It is estimated that the accumulated losses since 2018 as a result of the decrease in the value-added generated by Spanish wine exports exceed 300 million euros. In addition, the results suggest that the negative effects of COVID-19 are greater than the effects caused by the rest of the geopolitical changes.

15.
Sleep Med Rev ; 69: 101769, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36933344

RESUMEN

During the last decade quantitative and molecular genetic research on sleep has increased considerably. New behavioural genetics techniques have marked a new era for sleep research. This paper provides a summary of the most important findings from the last ten years, on the genetic and environmental influences on sleep and sleep disorders and their associations with health-related variables (including anxiety and depression) in humans. In this review we present a brief summary of the main methods in behaviour genetic research (such as twin and genome-wide association studies). We then discuss key research findings on: genetic and environmental influences on normal sleep and sleep disorders, as well as on the association between sleep and health variables (highlighting a substantial role for genes in individual differences in sleep and their associations with other variables). We end by discussing future lines of enquiry and drawing conclusions, including those focused on problems and misconceptions associated with research of this type. In this last decade our knowledge about genetic and environmental influences on sleep and its disorders has expanded. Both, twin and genome-wide association studies show that sleep and sleep disorders are substantially influenced by genetic factors and for the very first time multiple specific genetic variants have been associated with sleep traits and disorders.


Asunto(s)
Estudio de Asociación del Genoma Completo , Trastornos del Sueño-Vigilia , Humanos , Sueño/genética , Trastornos del Sueño-Vigilia/genética , Trastornos del Sueño-Vigilia/complicaciones , Investigación Genética , Biología Molecular
16.
Sleep Med ; 104: 105-112, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36934464

RESUMEN

STUDY OBJECTIVES: Isolated sleep paralysis is a benign but frightening condition characterised by a temporary inability to move at sleep onset or upon awakening. Despite the prevalence of this condition, little is known concerning its clinical features, associated demographic characteristics, and prevention as well as disruption strategies. METHODS: An online cross-sectional study was conducted. The sample comprised 3523 participants who had reported at least one lifetime episode of ISP and 3288 participants without a lifetime episode. Participants answered a survey including questions about sleep quality, sleep paralysis, and sleep paralysis prevention/disruption techniques. RESULTS: A total of 6811 participants were investigated (mean age = 46.9, SD = 15.4, age range = 18-89, 66.1% female). Those who reported experiencing ISP at least once during their lives reported longer sleep onset latencies, shorter sleep duration, and greater insomnia symptoms. Females (vs. male) and younger (vs. older) participants were more likely to experience ISP. Significant fear during episodes was reported by 76.0% of the participants. Most people (63.3%) who experienced ISP believed it to be caused by 'something in the brain'. A minority endorsed supernatural causes (7.1%). Five prevention strategies (e.g., changing sleep position, adjusting sleep patterns) with at least 60.0% effectiveness, and five disruption strategies (e.g., physical/bodily action, making noise) with varying degrees of effectiveness (ranging from 29.5 to 61.8) were identified through open-ended responses. CONCLUSIONS: ISP is associated with shorter sleep duration, longer sleep onset latency, and greater insomnia symptoms. The multiple prevention and disruption techniques identified in this study support existing treatment approaches and may inform subsequent treatment development. Implications for current diagnostic criteria are discussed.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Parálisis del Sueño , Trastornos del Sueño-Vigilia , Humanos , Masculino , Femenino , Adolescente , Persona de Mediana Edad , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Estudios Transversales , Sueño , Trastornos del Sueño-Vigilia/complicaciones , Percepción
17.
J Immunother Cancer ; 11(2)2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36854569

RESUMEN

BACKGROUND: Approximately one-third of diffuse large B cell lymphoma (DLBCL) patients exhibit co-expression of MYC and BCL2 (double-expressor lymphoma, DEL) and have a dismal prognosis. Targeted inhibition of the anti-apoptotic protein BCL2 with venetoclax (ABT-199) has been approved in multiple B-cell malignancies and is currently being investigated in clinical trials for DLBCL. Whether BCL2 anti-apoptotic function represents a multifaceted vulnerability for DEL-DLBCL, affecting both lymphoma B cells and T cells within the tumor microenvironment, remains to be elucidated. METHODS: Here, we present novel genetically engineered mice that preclinically recapitulate DEL-DLBCL lymphomagenesis, and evaluate their sensitivity ex vivo and in vivo to the promising combination of venetoclax with anti-CD20-based standard immunotherapy. RESULTS: Venetoclax treatment demonstrated specific killing of MYC+/BCL2+ lymphoma cells by licensing their intrinsically primed apoptosis, and showed previously unrecognized immunomodulatory activity by specifically enriching antigen-activated effector CD8 T cells infiltrating the tumors. Whereas DEL-DLBCL mice were refractory to venetoclax alone, inhibition of BCL2 significantly extended overall survival of mice that were simultaneously treated with a murine surrogate for anti-CD20 rituximab. CONCLUSIONS: These results suggest that the combination of anti-CD20-based immunotherapy and BCL2 inhibition leads to cooperative immunomodulatory effects and improved preclinical responses, which may offer promising therapeutic opportunities for DEL-DLBCL patients.


Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Inmunoterapia , Linfoma de Células B Grandes Difuso , Animales , Ratones , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Modelos Animales de Enfermedad , Inmunoterapia/métodos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2 , Microambiente Tumoral , Proteínas Proto-Oncogénicas c-myc
18.
J Sleep Res ; 32(4): e13810, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-36632033

RESUMEN

Previous studies have found significant associations between paranormal beliefs and sleep variables. However, these have been conducted on a small scale and are limited in the number of sleep variables investigated. This study aims to fill a gap in the literature by investigating paranormal beliefs in relation to a wide range of sleep variables in a large sample. Participants (N = 8853) completed a survey initiated by the BBC Focus Magazine. They reported on their demographics, sleep disturbances and paranormal beliefs. Poorer subjective sleep quality (lower sleep efficiency, longer sleep latency, shorter sleep duration and increased insomnia symptoms) was associated with greater endorsement of belief in: (1) the soul living on after death; (2) the existence of ghosts; (3) demons; (4) an ability for some people to communicate with the dead; (5) near-death experiences are evidence for life after death; and (6) aliens have visited earth. In addition, episodes of exploding head syndrome and isolated sleep paralysis were associated with the belief that aliens have visited earth. Isolated sleep paralysis was also associated with the belief that near-death experiences are evidence for life after death. Findings obtained here indicate that there are associations between beliefs in the paranormal and various sleep variables. This information could potentially better equip us to support sleep via psychoeducation. Mechanisms underlying these associations are likely complex, and need to be further explored to fully understand why people sometimes report "things that go bump in the night".


Asunto(s)
Parapsicología , Parasomnias , Trastornos del Inicio y del Mantenimiento del Sueño , Parálisis del Sueño , Humanos , Sueño
19.
J Child Psychol Psychiatry ; 64(2): 213-216, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36636905

RESUMEN

There are strong arguments for standardizing therapies for mental health difficulties in young people and for the development of digital therapies. At the same time, the importance of personalized treatments is also increasingly apparent. In this editorial, we discuss challenges and the continued need to find the sweet spot between standardization and personalization when it comes to therapies for mental health difficulties. We illustrate our discussion with reference to insomnia in adolescents/young adults as well as the chronic health condition type 1 diabetes.


Asunto(s)
Salud Mental , Trastornos del Inicio y del Mantenimiento del Sueño , Adolescente , Adulto Joven , Humanos , Estándares de Referencia
20.
Environ Res ; 222: 115310, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36693461

RESUMEN

Studying the thermodynamic properties of soil organic matter is a developing field that involves the measurement of the energy stored by the soil. Quantifying soil energy content is still challenging despite different methodological approaches are available to calculate that value. One of the options is the proximate analysis following the guidelines for the energetic characterization of biomass. However, proximate analyses are still unexplored for soils. In this paper, we investigate the potential of this analysis to contribute to study soil from a thermodynamic perspective. With that goal, 31 soil samples collected in mature oak forests following a depth transect were used for elemental, thermal and proximate analysis. Proximate analyses and energetic characterization were performed by simultaneous thermogravimetry and differential scanning calorimetry. These methods allowed fragmentation of the soil organic matter in water content, volatile matter, fixed carbon, and ash, as well as the quantification of the soil organic matter and energy content. Pearson's correlation showed significant relations among the proximate, the elemental components of soils and the energy. The equations relating all of these variables were calculated for soils from oak forests by partial least squares analysis. Equations representing the relationship between energy and the proximate fractions provide an additional alternative to calculate the heat of combustion of the soil organic matter. This value is the essential step for the thermodynamic characterization of soils.


Asunto(s)
Ecosistema , Quercus , Suelo/química , Bosques , Carbono/análisis , Minerales/análisis , Termodinámica
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