ABSTRACT
Dysregulation of RNA splicing contributes to both rare and complex diseases. RNA-sequencing data from human tissues has shown that this process can be inaccurate, resulting in the presence of novel introns detected at low frequency across samples and within an individual. To enable the full spectrum of intron use to be explored, we have developed IntroVerse, which offers an extensive catalogue on the splicing of 332,571 annotated introns and a linked set of 4,679,474 novel junctions covering 32,669 different genes. This dataset has been generated through the analysis of 17,510 human control RNA samples from 54 tissues provided by the Genotype-Tissue Expression Consortium. IntroVerse has two unique features: (i) it provides a complete catalogue of novel junctions and (ii) each novel junction has been assigned to a specific annotated intron. This unique, hierarchical structure offers multiple uses, including the identification of novel transcripts from known genes and their tissue-specific usage, and the assessment of background splicing noise for introns thought to be mis-spliced in disease states. IntroVerse provides a user-friendly web interface and is freely available at https://rytenlab.com/browser/app/introverse.
Subject(s)
Databases, Genetic , Introns , RNA Splicing , Humans , Alternative Splicing , Base Sequence , Introns/genetics , RNA , RNA Splicing/geneticsABSTRACT
Letermovir for CMV prevention in CMV-seropositive adults undergoing allo-HCT was implemented at our program in 2021. This study investigates the results from the use of letermovir. The study includes all the 140 CMV-seropositive patients who underwent an allo-HCT during the years 2020, 2021, and 2022 at our institution. Thirty-eight (27.4%) of these patients received letermovir, administered from day + 7 to day + 100 and restarted if patients were on treatment with steroids. The day + 180 and 1-year cumulative incidences of CMV reactivation were 5.3% and 12.1% for patients who received letermovir and 52.9% and 53.9% for those who did not (P < 0.001) (HR 0.19, P < 0.001). Four (10.5%) of these thirty-eight patients had a CMV reactivation, but only 2 (5.3%) cases occurred during the administration of letermovir. During the first year after allo-HCT, 13 (9.2%) patients had CMV disease; the day + 180 and 1-year cumulative incidences were 2.6% and 6.0% for patients who received letermovir and 9.9% and 12.3% for those who did not (P = 0.254) (HR 1.01, P = 0.458). Two (4.2%) of the patients included in the letermovir group had CMV disease, but both of them after letermovir discontinuation. Letermovir induced a protective effect on CMV reactivation risk, but its use was not associated with a significant reduction of CMV disease. The fact that the CMV disease in patients who received letermovir occurred after the discontinuation of the drug, questions whether CMV prophylaxis should be used in patients with high risk for CMV reactivation or disease.
Subject(s)
Acetates , Cytomegalovirus Infections , Hematopoietic Stem Cell Transplantation , Quinazolines , Adult , Humans , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/etiology , Cytomegalovirus Infections/prevention & control , Cytomegalovirus , Antiviral Agents/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
Genetic variants conferring risks for Parkinson's disease have been highlighted through genome-wide association studies, yet exploration of their specific disease mechanisms is lacking. Two Parkinson's disease candidate genes, KAT8 and KANSL1, identified through genome-wide studies and a PINK1-mitophagy screen, encode part of the histone acetylating non-specific lethal complex. This complex localizes to the nucleus, where it plays a role in transcriptional activation, and to mitochondria, where it has been suggested to have a role in mitochondrial transcription. In this study, we sought to identify whether the non-specific lethal complex has potential regulatory relationships with other genes associated with Parkinson's disease in human brain. Correlation in the expression of non-specific lethal genes and Parkinson's disease-associated genes was investigated in primary gene co-expression networks using publicly-available transcriptomic data from multiple brain regions (provided by the Genotype-Tissue Expression Consortium and UK Brain Expression Consortium), whilst secondary networks were used to examine cell type specificity. Reverse engineering of gene regulatory networks generated regulons of the complex, which were tested for heritability using stratified linkage disequilibrium score regression. Prioritized gene targets were then validated in vitro using a QuantiGene multiplex assay and publicly-available chromatin immunoprecipitation-sequencing data. Significant clustering of non-specific lethal genes was revealed alongside Parkinson's disease-associated genes in frontal cortex primary co-expression modules, amongst other brain regions. Both primary and secondary co-expression modules containing these genes were enriched for mainly neuronal cell types. Regulons of the complex contained Parkinson's disease-associated genes and were enriched for biological pathways genetically linked to disease. When examined in a neuroblastoma cell line, 41% of prioritized gene targets showed significant changes in mRNA expression following KANSL1 or KAT8 perturbation. KANSL1 and H4K8 chromatin immunoprecipitation-sequencing data demonstrated non-specific lethal complex activity at many of these genes. In conclusion, genes encoding the non-specific lethal complex are highly correlated with and regulate genes associated with Parkinson's disease. Overall, these findings reveal a potentially wider role for this protein complex in regulating genes and pathways implicated in Parkinson's disease.
Subject(s)
Parkinson Disease , Humans , Parkinson Disease/genetics , Parkinson Disease/metabolism , Genome-Wide Association Study , Mitochondria/metabolism , Brain/metabolism , Gene Regulatory NetworksABSTRACT
Improvements in functional genomic annotation have led to a critical mass of neurogenetic discoveries. This is exemplified in hereditary ataxia, a heterogeneous group of disorders characterised by incoordination from cerebellar dysfunction. Associated pathogenic variants in more than 300 genes have been described, leading to a detailed genetic classification partitioned by age-of-onset. Despite these advances, up to 75% of patients with ataxia remain molecularly undiagnosed even following whole genome sequencing, as exemplified in the 100 000 Genomes Project. This study aimed to understand whether we can improve our knowledge of the genetic architecture of hereditary ataxia by leveraging functional genomic annotations, and as a result, generate insights and strategies that raise the diagnostic yield. To achieve these aims, we used publicly-available multi-omics data to generate 294 genic features, capturing information relating to a gene's structure, genetic variation, tissue-specific, cell-type-specific and temporal expression, as well as protein products of a gene. We studied these features across genes typically causing childhood-onset, adult-onset or both types of disease first individually, then collectively. This led to the generation of testable hypotheses which we investigated using whole genome sequencing data from up to 2182 individuals presenting with ataxia and 6658 non-neurological probands recruited in the 100 000 Genomes Project. Using this approach, we demonstrated a high short tandem repeat (STR) density within childhood-onset genes suggesting that we may be missing pathogenic repeat expansions within this cohort. This was verified in both childhood- and adult-onset ataxia patients from the 100 000 Genomes Project who were unexpectedly found to have a trend for higher repeat sizes even at naturally-occurring STRs within known ataxia genes, implying a role for STRs in pathogenesis. Using unsupervised analysis, we found significant similarities in genomic annotation across the gene panels, which suggested adult- and childhood-onset patients should be screened using a common diagnostic gene set. We tested this within the 100 000 Genomes Project by assessing the burden of pathogenic variants among childhood-onset genes in adult-onset patients and vice versa. This demonstrated a significantly higher burden of rare, potentially pathogenic variants in conventional childhood-onset genes among individuals with adult-onset ataxia. Our analysis has implications for the current clinical practice in genetic testing for hereditary ataxia. We suggest that the diagnostic rate for hereditary ataxia could be increased by removing the age-of-onset partition, and through a modified screening for repeat expansions in naturally-occurring STRs within known ataxia-associated genes, in effect treating these regions as candidate pathogenic loci.
Subject(s)
Cerebellar Ataxia , Spinocerebellar Degenerations , Adult , Humans , Spinocerebellar Degenerations/genetics , Cerebellar Ataxia/diagnosis , Cerebellar Ataxia/genetics , Ataxia/diagnosis , Ataxia/genetics , Genomics , Genetic TestingABSTRACT
This corrects the article DOI: 10.1038/nature22964.
ABSTRACT
The functional traits of organisms within multispecies assemblages regulate biodiversity effects on ecosystem functioning. Yet how traits should assemble to boost multiple ecosystem functions simultaneously (multifunctionality) remains poorly explored. In a multibiome litter experiment covering most of the global variation in leaf trait spectra, we showed that three dimensions of functional diversity (dispersion, rarity, and evenness) explained up to 66% of variations in multifunctionality, although the dominant species and their traits remained an important predictor. While high dispersion impeded multifunctionality, increasing the evenness among functionally dissimilar species was a key dimension to promote higher multifunctionality and to reduce the abundance of plant pathogens. Because too-dissimilar species could have negative effects on ecosystems, our results highlight the need for not only diverse but also functionally even assemblages to promote multifunctionality. The effect of functionally rare species strongly shifted from positive to negative depending on their trait differences with the dominant species. Simultaneously managing the dispersion, evenness, and rarity in multispecies assemblages could be used to design assemblages aimed at maximizing multifunctionality independently of the biome, the identity of dominant species, or the range of trait values considered. Functional evenness and rarity offer promise to improve the management of terrestrial ecosystems and to limit plant disease risks.
Subject(s)
Biodiversity , Plant Leaves/physiology , Biomass , Carbon Cycle , Plant Leaves/classification , Plant Physiological PhenomenaABSTRACT
OBJECTIVE: To compare the stress distribution and total strain applied to the dentition, periodontal ligament (PDL) and cortical and trabecular bones by three Class II correctors using finite element analysis. DESIGN: Three-dimensional analysis of stresses and total strain of the dentition with three Class II correctors. SETTING: Computational study. METHODS: Three-dimensional finite element models of Class II elastics, the Forsus Fatigue Resistant Device (FRD) and the Carriere Motion Appliance (CMA) were constructed from a cone-beam computed tomography (CBTC) image of an orthodontic Class II patient. The distribution of stress (von Mises and principal stress) and the total strain (mm) in maxillo-mandibular dentition, PDL, cortical and trabecular bone were analysed. RESULTS: The highest von Mises yield and the maximum principal stress in the three models were found at the teeth, followed by the cortical bone, trabecular bone and PDL. The maximum stress and total deformation were located at the upper canines and lower molars in the Class II elastics and CMA models, in the upper first molars in the Forsus FRD and CMA, and in the lower first premolars in the Forsus FRD. In addition, stress was distributed in the anterior and posterior regions of the teeth, and the total deformation was found in the distal direction in the upper arch and in the mesial direction in the lower arch. CONCLUSION: The stress concentrations in the three models were located close to the active components of each appliance, producing specific patterns of stress distribution and displacement that should be taken into account when planning the type of appliance to be used for the correction of the Class II malocclusion.
Subject(s)
Malocclusion, Angle Class II , Tooth , Humans , Finite Element Analysis , Malocclusion, Angle Class II/diagnostic imaging , Malocclusion, Angle Class II/therapy , Molar/diagnostic imaging , Cone-Beam Computed Tomography/methodsABSTRACT
MOTIVATION: The advent of long-read sequencing technologies has increased demand for the visualization and interpretation of transcripts. However, tools that perform such visualizations remain inflexible and lack the ability to easily identify differences between transcript structures. Here, we introduce ggtranscript, an R package that provides a fast and flexible method to visualize and compare transcripts. As a ggplot2 extension, ggtranscript inherits the functionality and familiarity of ggplot2 making it easy to use. AVAILABILITY AND IMPLEMENTATION: ggtranscript is an R package available at https://github.com/dzhang32/ggtranscript (DOI: https://doi.org/10.5281/zenodo.6374061) via an open-source MIT licence. Further documentation is available at https://dzhang32.github.io/ggtranscript/.
Subject(s)
Software , Sequence Analysis, DNA/methods , Protein Isoforms/geneticsABSTRACT
Activation of the PTEN-PI3K-mTORC1 pathway consolidates metabolic programs that sustain cancer cell growth and proliferation. Here we show that mechanistic target of rapamycin complex 1 (mTORC1) regulates polyamine dynamics, a metabolic route that is essential for oncogenicity. By using integrative metabolomics in a mouse model and human biopsies of prostate cancer, we identify alterations in tumours affecting the production of decarboxylated S-adenosylmethionine (dcSAM) and polyamine synthesis. Mechanistically, this metabolic rewiring stems from mTORC1-dependent regulation of S-adenosylmethionine decarboxylase 1 (AMD1) stability. This novel molecular regulation is validated in mouse and human cancer specimens. AMD1 is upregulated in human prostate cancer with activated mTORC1. Conversely, samples from a clinical trial with the mTORC1 inhibitor everolimus exhibit a predominant decrease in AMD1 immunoreactivity that is associated with a decrease in proliferation, in line with the requirement of dcSAM production for oncogenicity. These findings provide fundamental information about the complex regulatory landscape controlled by mTORC1 to integrate and translate growth signals into an oncogenic metabolic program.
Subject(s)
Adenosylmethionine Decarboxylase/metabolism , Multiprotein Complexes/metabolism , Polyamines/metabolism , Prostatic Neoplasms/metabolism , TOR Serine-Threonine Kinases/metabolism , Adenosylmethionine Decarboxylase/immunology , Animals , Cell Proliferation , Enzyme Activation , Everolimus/therapeutic use , Humans , Male , Mechanistic Target of Rapamycin Complex 1 , Metabolomics , Mice , Multiprotein Complexes/antagonists & inhibitors , PTEN Phosphohydrolase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Protein Stability , S-Adenosylmethionine/analogs & derivatives , S-Adenosylmethionine/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitorsABSTRACT
MOTIVATION: Co-expression networks are a powerful gene expression analysis method to study how genes co-express together in clusters with functional coherence that usually resemble specific cell type behavior for the genes involved. They can be applied to bulk-tissue gene expression profiling and assign function, and usually cell type specificity, to a high percentage of the gene pool used to construct the network. One of the limitations of this method is that each gene is predicted to play a role in a specific set of coherent functions in a single cell type (i.e. at most we get a single
Subject(s)
Gene Regulatory Networks , Software , Humans , Brain , Gene Expression Profiling/methodsABSTRACT
OBJECTIVE: To assess changes in voiding phase, especially urethral resistance after post-prostatectomy urinary incontinence (PPI) treatment with the Adjustable TransObturator Male System (ATOMS). MATERIAL AND METHODS: A longitudinal prospective study was performed on 45 men treated with ATOMS for PPI, with the intention to evaluate the changes produced by the implant on the voiding phase. Patients with preoperative urodynamic study were offered postoperative urodynamic evaluation, and both studies were compared. The following urodynamic date were evaluated: maximum voiding detrusor pressure, detrusor pressure at maximum flow rate, maximum flow rate (Qmax), voiding volume, post-void residue, bladder outlet obstruction index (BOOI), urethral resistance factor (URA), and bladder contractility index (BCI). The statistical analysis used were the mean comparison test for dependent groups (Student's t test) for parametric variables and the Wilcoxon test for non-parametric variables. The signification level was set at 95% bilateral. RESULTS: A total of 37 patients (82.2%) used zero pads/day at the time of urodynamic postoperative evaluation and pad-test evolved from 592 ± 289 ml baseline to 25 ± 40 ml (p = 0.0001). Significant differences were observed in Qmax (15 ± 8.3 before and 11 ± 8.3 after surgery; p = 0.008), voiding volume (282 ± 130.7 before and 184 ± 99.92 after surgery). BOOI (-12 ± 23.9 before and -2 ± 21.4 after surgery; p = 0.025) and BCI (93 ± 46.4 before and 76 ± 46.0 after surgery; p = 0.044). In no case did we observe postoperative bladder outlet obstruction, according to URA parameter below 29 cm H2 O in all cases. There was not a significant variation either in post-void urinary residual volume (15 ± 47.4 before and 14 ± 24.2 after surgery, p = 0.867). CONCLUSIONS: The ATOMS implant induces a decrease of Qmax, voided volume, and bladder contractility and an increase of BOOI. However, our findings suggest that ATOMS device does not cause bladder outlet obstruction.
Subject(s)
Urinary Bladder Neck Obstruction , Urinary Incontinence , Humans , Male , Prospective Studies , Prostatectomy/adverse effects , Urinary Bladder Neck Obstruction/etiology , Urinary Bladder Neck Obstruction/surgery , Urinary Incontinence/complications , Urination , UrodynamicsABSTRACT
INTRODUCTION: The purpose of this study was to compare the thickness and length of the zygomatic process (ZP) of the maxilla, infrazygomatic crest area, and mandibular buccal shelf by sex and age. METHODS: Cone-beam computed tomography images of 128 subjects were divided into 3 groups: (1) 22 female and 19 male subjects aged 9-13 years, (2) 27 female and 20 male subjects aged 14-23 years, and (3) 20 female and 20 male subjects aged 24-50 years. A previously calibrated operator was used to take all measurements of the zygomatic process vertical bone thickness, zygomatic process horizontal bone length, zygomatic process/cementoenamel length (ZP/CEJL), infrazygomatic crest region bone thickness (IZCBT), infrazygomatic crest region bone length (IZCL), and mandibular buccal shelf bone thickness. Analysis of variance and Kruskal-Wallis tests were used for statistical analyses. Two-way analysis of variance was used for variables with significant differences by sex (P <0.002 as determined by Bonferroni correction for multiple comparisons). RESULTS: Differences by sex were only found for IZCL in the maxillary second premolar and first molar (U5-U6) and the maxillary first molar (U6). Significant differences were observed among age groups for ZP/CEJL, IZCBT in U5-U6 and U6, and IZCL in U6-distal. CONCLUSIONS: The results suggest that ZP/CEJL and IZCL are larger in adults than in younger subjects, whereas IZCBT is smaller in adults than in younger subjects.
Subject(s)
Maxilla , Orthodontic Anchorage Procedures , Adolescent , Adult , Bone Screws , Child , Cone-Beam Computed Tomography/methods , Female , Humans , Male , Maxilla/diagnostic imaging , Middle Aged , Orthodontic Anchorage Procedures/methods , Young Adult , Zygoma/diagnostic imagingABSTRACT
Obesity is one of the most important health problems nowadays. In addition to the direct physical consequences, it is also a risk factor in the development of psychological (Eating disorders, body dissatisfaction, depression, anxiety, etc.) and social problems. Among there, body dissatisfaction is key for development and maintenance of such problems. OBJECTIVE: to deepen the effectiveness of the body exposure treatment, both in its pure form and guided modality in subjective, psychological and attentional levels in people with body dissatisfaction and obesity. METHODS: Evaluations were carried out in a total of 16 women with obesity and body dissatisfaction at the beginning and end of 6 treatment sessions of pure exposure in front of the mirror. The changes experienced at the subjective level (questionnaires and subjective discomfort during the sessions) and psychophysiological (eye-tracking and heart rate) were analyzed. RESULTS: Pure exposure treatment reduces negative thoughts and emotions towards the body itself, as well as the experienced discomfort towards the most conflictive parts. Selective attention to those parts of the body classified as uglier by the participants (especially the rear view of the body) show a decrease in physiological reactivity. CONCLUSIONS: Pure exposure treatment seems to be effective in reducing subjective and psychological symptoms associated with body dissatisfaction in people with obesity, this technique could be considered a good choice for the treatment of body dissatisfaction. This step is essential to guarantee the long-term therapeutic success of any other treatment (nutritional or/and physical activity) in the future.
Subject(s)
Attentional Bias , Body Dissatisfaction , Body Image/psychology , Emotions , Female , Humans , Obesity/therapyABSTRACT
Argininosuccinate lyase (ASL) is essential for the NO-dependent regulation of tyrosine hydroxylase (TH) and thus for catecholamine production. Using a conditional mouse model with loss of ASL in catecholamine neurons, we demonstrate that ASL is expressed in dopaminergic neurons in the substantia nigra pars compacta, including the ALDH1A1 + subpopulation that is pivotal for the pathogenesis of Parkinson disease (PD). Neuronal loss of ASL results in catecholamine deficiency, in accumulation and formation of tyrosine aggregates, in elevation of α-synuclein, and phenotypically in motor and cognitive deficits. NO supplementation rescues the formation of aggregates as well as the motor deficiencies. Our data point to a potential metabolic link between accumulations of tyrosine and seeding of pathological aggregates in neurons as initiators for the pathological processes involved in neurodegeneration. Hence, interventions in tyrosine metabolism via regulation of NO levels may be therapeutic beneficial for the treatment of catecholamine-related neurodegenerative disorders.
Subject(s)
Aldehyde Dehydrogenase 1 Family/genetics , Aldehyde Dehydrogenase 1 Family/metabolism , Argininosuccinate Lyase/genetics , Argininosuccinate Lyase/metabolism , Dopaminergic Neurons/metabolism , Parkinson Disease/genetics , Parkinson Disease/metabolism , Animals , Disease Models, Animal , Humans , Mice , Phenotype , Retinal Dehydrogenase/genetics , Retinal Dehydrogenase/metabolismABSTRACT
OBJECTIVE: To assess the efficacy and safety of Adjustable Transobturator Male System (ATOMS) compared to male Readjustment Mechanical External (REMEEX) system for post-prostatectomy incontinence (PPI). MATERIAL AND METHODS: A systematic review and meta-analysis on adjustable device ATOMS compared to male REMEEX is presented. Studies on female or neurogenic incontinence were excluded. Primary objectives were evaluation of dryness (the proportion of patients with no-pad or one safety pad/day after device adjustment) and improvement between devices. Secondary objectives were complications and explant rate. They were estimated using a random-effect model. Statistical heterogeneity among studies was assessed using Cochran's Q test, Higgins's I2 statistics and tau2. RESULTS: Combined data of 29 observational studies with 1919 patients showed an equivalent proportion of patients treated with radical prostatectomy (p = .125) and previous radiation (p = .126). Dryness rate was 69.3% for ATOMS and 53.4% for male REEMEX (p = .008). Improvement rate was 90.8% for ATOMS and 80.2% for REMEEX (p = .007). Complication rate was 18.9% for ATOMS and 35.8% for REMEEX (p = .096) and explant rate was 5.5% for ATOMS and 13.9% for REMEEX (p = .027). Significant heterogeneity was evidenced, due to absence of randomized studies, variable incontinence severity baseline, difficulties for a common reporting of complications and difference in the follow-up. Differences observed between devices remained statistically significant when only studies with silicone-covered scrotal port (SSP) ATOMS and male REMEEX system II were considered. CONCLUSIONS: Despite the absence of direct comparison and the limitations observed ATOMS appears more effective than male REMEEX to treat PPI, and with less explant rate as reported in the literature.
Subject(s)
Postoperative Complications/surgery , Prostatectomy , Suburethral Slings , Urinary Incontinence/surgery , Equipment and Supplies , Humans , Postoperative Complications/etiology , Prostatectomy/adverse effects , Suburethral Slings/adverse effects , Treatment Outcome , Urinary Incontinence/etiologyABSTRACT
Dystonia is a neurological disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and postures, often occurring in absence of any structural brain abnormality. Psychiatric comorbidities, including anxiety, depression, obsessive-compulsive disorder and schizophrenia, are frequent in patients with dystonia. While mutations in a fast-growing number of genes have been linked to Mendelian forms of dystonia, the cellular, anatomical, and molecular basis remains unknown for most genetic forms of dystonia, as does its genetic and biological relationship to neuropsychiatric disorders. Here we applied an unbiased systems-biology approach to explore the cellular specificity of all currently known dystonia-associated genes, predict their functional relationships, and test whether dystonia and neuropsychiatric disorders share a genetic relationship. To determine the cellular specificity of dystonia-associated genes in the brain, single-nuclear transcriptomic data derived from mouse brain was used together with expression-weighted cell-type enrichment. To identify functional relationships among dystonia-associated genes, we determined the enrichment of these genes in co-expression networks constructed from 10 human brain regions. Stratified linkage-disequilibrium score regression was used to test whether co-expression modules enriched for dystonia-associated genes significantly contribute to the heritability of anxiety, major depressive disorder, obsessive-compulsive disorder, schizophrenia, and Parkinson's disease. Dystonia-associated genes were significantly enriched in adult nigral dopaminergic neurons and striatal medium spiny neurons. Furthermore, 4 of 220 gene co-expression modules tested were significantly enriched for the dystonia-associated genes. The identified modules were derived from the substantia nigra, putamen, frontal cortex, and white matter, and were all significantly enriched for genes associated with synaptic function. Finally, we demonstrate significant enrichments of the heritability of major depressive disorder, obsessive-compulsive disorder and schizophrenia within the putamen and white matter modules, and a significant enrichment of the heritability of Parkinson's disease within the substantia nigra module. In conclusion, multiple dystonia-associated genes interact and contribute to pathogenesis likely through dysregulation of synaptic signalling in striatal medium spiny neurons, adult nigral dopaminergic neurons and frontal cortical neurons. Furthermore, the enrichment of the heritability of psychiatric disorders in the co-expression modules enriched for dystonia-associated genes indicates that psychiatric symptoms associated with dystonia are likely to be intrinsic to its pathophysiology.
Subject(s)
Dystonic Disorders/genetics , Gene Regulatory Networks/genetics , Mental Disorders/genetics , Neurons/physiology , Dystonic Disorders/diagnosis , Dystonic Disorders/epidemiology , Humans , Mental Disorders/diagnosis , Mental Disorders/epidemiologyABSTRACT
AIM: To know, in the population over 70, independent for walking, the prevalence of the concern to fall according to the short version of the Short Falls Efficacy Scale-International (FES-I) questionnaire, in old people living in the community and their associated factors. DESIGN: Cross-sectional study. LOCATION: Centro de Salud El Greco, Getafe, Madrid, Spain. PARTICIPANTS: 189 patients ≥70years with a Barthel ≥60, independent for walking (walk 45minutes without help or with a cane). The study was offered to a total of 328 people, of these accepted 217 and rejected 111. MAIN MEASUREMENTS: The dependent variable, fear of falling (FOF), was evaluated by means of the short FES-I questionnaire, considering as a cut-off point for the positive screening of the MC a score ≥11. As independent variables we considered: Barthel index, Downton scale, the Short Physical Performance Battery (SPPB) fragility test, falls in the last year, injuries associated with falls, time since the last fall, sensory deficit, use of gait devices, comorbidity and pharmacological treatment. RESULTS: The prevalence of FOF was 42.9% (95%CI: 35.5-50.2). The factors associated with FOF in the final multivariate analysis were: female sex, living alone, high risk of falls, presence of frailty (SPPB≤9), use of hypotensive drugs, and injuries associated with previous falls. CONCLUSIONS: The prevalence of FOF in older people is high. Primary Care professionals should systematize the screening of this health problem, prioritizing especially in people who present the following risk factors: being a woman, living alone, having a low score on the SPPB (as an indicator of frailty) or presenting a high risk of falls.
Subject(s)
Fear , Independent Living , Aged , Cross-Sectional Studies , Female , Humans , Prevalence , Risk FactorsABSTRACT
OBJECTIVE: To evaluate whether urodynamic voiding risk factors can be predictive of failure of postprostatectomy urinary incontinence (PPI) treatment with adjustable transobturator male system (ATOMS). MATERIALS AND METHODS: We carried out a longitudinal study on 77 males treated for PPI with ATOMS. Patients were submitted preoperatively to a urodynamic study. The postoperative outcome was checked by pad-test. Treatment success was defined as daily pad-test below 10 mL. Statistical analysis used were Fisher exact test, χ2 lineal by lineal test, Student t test, and logistic regression analysis. The signification level was set at 95% bilateral. RESULTS: Treatment was successful in 54 patients (70%) achieving continence. The urodynamic parameters that related to postoperative continence outcome were the cystometric bladder capacity (direct relationship with continence (P = .019), type of voiding (more probability to achieve continence in patients who voided voluntarily followed by patients with involuntary voiding and abdominal straining voiding) (P = .034), Bladder Outlet Obstruction Index (BOOI) (inversely related with continence) (P = .025), and maximum voiding abdominal pressure (inversely related with continence) (P = .049). Multivariate analysis showed that cystometric bladder capacity (odds ratio [OR], 1.01; confidence interval [CI], 1.02-1.00), BOOI (OR, 0.97; CI, 0.99-0.94), and maximum abdominal bladder pressure (OR, 0.97; CI, 0.98-0.94) were independent risk factors to predict treatment success after ATOMS implant. CONCLUSIONS: The study of functional voiding parameters is useful to know the risk factors that influence postoperative outcome of PPI with ATOMS device. These findings could be of primary importance to facilitate optimum patient selection for this implant and therefore improve operative results.
Subject(s)
Prostatectomy/adverse effects , Suburethral Slings , Urinary Bladder/physiopathology , Urinary Incontinence/physiopathology , Urinary Sphincter, Artificial , Urination/physiology , Urodynamics/physiology , Aged , Humans , Longitudinal Studies , Male , Middle Aged , Treatment Outcome , Urinary Incontinence/etiology , Urinary Incontinence/surgeryABSTRACT
AIM: The aim of this study is to evaluate long-term durability and effectiveness of the adjustable transobturator male system (ATOMS). MATERIALS AND METHODS: The retrospective multicenter Iberian ATOMS study (n = 215) was updated to evaluate long-term continence status, complications, explants, and secondary treatments. Mean follow-up from surgery to March 2020 was 60.6 ± 18.4 months (range, 39-91). Eleven patients deceased of an unrelated causes. Kaplan-Meier curves were performed to evaluate device durability and incontinence free of recurrence interval. The multivariate analysis defined the population at risk of device explant. RESULTS: A total of 155 patients were dry at the last follow-up visit (72.1%); 99 (46%) used no pads and 56 (26%) used a security pad/day with urine loss less than 10 mL; 96% of dry patients after adjustment remained free of incontinence 1 year later, 93.6% 2 years later, 91.1% 3 years later, 89.2% 5 years later, and 86.7% 8 years later. Complications during follow-up occurred in 43 of 215 (20%). In total, 25 (11.6%) devices were explanted and causes were inefficacy 11 (44%), inefficacy and pain 3 (12%), port erosion 10 (40%), and wound infection 1 (4%). The secondary implant was performed in 11 (5.1%) cases, 6 artificial urinary sphincter and 5 repeated ATOMS. Time to explant was associated to complications (P < .0001), baseline stress urinary incontinence (SUI) severity (P = .01), and former irradiation (P = .03). Multivariate analysis revealed complications (hazard ratio [HR] = 8.71; 3.83-19.82), baseline SUI severity (>5 compared to 1-2 pads/day; HR = 14.9; 1.87-125), and irradiation before ATOMS (HR = 2.26; 1.02-5.18) predicted earlier ATOMS explant. Three cases received radiation after implant without complication. CONCLUSIONS: ATOMS device is efficacious and safe in the long term. Determinants for device explant include complications, baseline severity of incontinence, and previous irradiation. Currently, the durability of the device after 5 years is reassuring.
Subject(s)
Prosthesis Design , Suburethral Slings , Urinary Incontinence, Stress/surgery , Urinary Sphincter, Artificial , Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Prostatectomy/adverse effects , Retrospective Studies , Treatment Outcome , Urinary Incontinence, Stress/etiologyABSTRACT
This study aimed to examine the psychophysiological changes resulting from two mirror exposure treatments that are effective at reducing body dissatisfaction. Thirty-five university women with body dissatisfaction and subclinical eating disorders were randomly assigned to one of two groups: pure (n = 17) or guided exposure (n = 18). The participants received six sessions of treatment. Their thoughts, feelings and avoidance behaviours were assessed after each session. Their subjective discomfort, heart rate and skin conductance were assessed within the sessions. Both groups showed improvement in cognitive-affective and avoidance behaviour symptoms. Nevertheless, the pure exposure group showed faster habituation of subjective discomfort and a greater physiological response than the guided exposure group. These findings suggest that both procedures are effective interventions for improving body image disturbances, although psychophysiological changes observed within session suggest that each technique would act through different processes. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.