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The Department of Defense (DoD) requires both current and projected estimates of the size of its workforce population with specific categories of disabilities. These estimates support the requirements under the Rehabilitation Act of 1973 as well as the goals outlined in multiple executive orders, including Executive Order 14035, directing DoD to hire employees with disabilities and provide them with reasonable accommodations. These estimates are necessary to determine the assistive technology (AT) required and its anticipated costs through 2031. AT also furthers DoD's goals in aiding the recovery and retention of injured service members, as well as the broader DoD and U.S. Department of Veteran Affairs (VA) community in aiding in the post-service employment of service members who are medically separating. Thus, the authors seek to estimate the potential demand for AT from these groups. The authors give projections of the DoD civilian employee population-and of injured and wounded service members-with specific disabilities categorized by DoD's centralized AT procurer (hearing, vision, cognitive, and dexterity disabilities), as well as the potential anticipated requests for AT by these populations and their costs between 2021 and 2031.
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BACKGROUND: The US population over the age of 65 is expected to double by the year 2050. Concordantly, the incidence of dementia is projected to increase. The subclinical stage of dementia begins years before signs and symptoms appear. Early detection of cognitive impairment and/or cognitive decline may allow for interventions to slow its progression. Furthermore, early detection may allow for implementation of care plans that may affect the quality of life of those affected and their caregivers. OBJECTIVE: We sought to determine the accuracy and validity of BrainCheck Memory as a diagnostic aid for age-related cognitive impairment, as compared against physician diagnosis and other commonly used neurocognitive screening tests, including the Saint Louis University Mental Status (SLUMS) exam, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). METHODS: We tested 583 volunteers over the age of 49 from various community centers and living facilities in Houston, Texas. The volunteers were divided into five cohorts: a normative population and four comparison groups for the SLUMS exam, the MMSE, the MoCA, and physician diagnosis. Each comparison group completed their respective assessment and BrainCheck Memory. RESULTS: A total of 398 subjects were included in the normative population. A total of 84 participants were in the SLUMS exam cohort, 51 in the MMSE cohort, 35 in the MoCA cohort, and 18 in the physician cohort. BrainCheck Memory assessments were significantly correlated to the SLUMS exam, with coefficients ranging from .5 to .7. Correlation coefficients for the MMSE and BrainCheck and the MoCA and BrainCheck were also significant. Of the 18 subjects evaluated by a physician, 9 (50%) were healthy, 6 (33%) were moderately impaired, and 3 (17%) were severely impaired. A significant difference was found between the severely and moderately impaired subjects and the healthy subjects (P=.02). We derived a BrainCheck Memory composite score that showed stronger correlations with the standard assessments as compared to the individual BrainCheck assessments. Receiver operating characteristic (ROC) curve analysis of this composite score found a sensitivity of 81% and a specificity of 94%. CONCLUSIONS: BrainCheck Memory provides a sensitive and specific metric for age-related cognitive impairment in older adults, with the advantages of a mobile, digital, and easy-to-use test. TRIAL REGISTRATION: ClinicalTrials.gov NCT03608722; https://clinicaltrials.gov/ct2/show/NCT03608722 (Archived by WebCite at http://www.webcitation.org/76JLoYUGf).
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To determine the impact of nutritional status and risk factors for undernutrition based on the changes in functional outcomes and rehabilitation success, defined as the ability of older adults to return as close as possible to their original functional state. Retrospective cohort study among 107 rehabilitation patients, aged ≥65 y. Data included demographics, Functional Independence Measure (FIM), Short Nutritional Assessment Questionnaire (SNAQ), reported weight, Mini-Mental Status Examination (MMSE), and Cumulative Illness Rating-Scale for Geriatrics (CIRS-G). Rehabilitation success was determined by delta-FIM. Higher vs. lower functioning patients were younger, had shorter hospitalization, and lower CIRS-G score with higher mean MMSE. Delta-FIM was significantly higher in patients with low malnutrition risk (SNAQ): 14.2 ± 10.5 vs. 6.9 ± 13.9 in undernourished patients, those who did not lose weight 14.5 ± 10.5 vs. 5.6 ± 12.8 in patients who lost weight with normal dietary intake, normal albumin, and lower CIES-G. Patients who achieved functional independence, FIMDC ≥90, ate normally and experienced less "appetite loss" [40.5% vs. 68.4%; P = 0.048]. Weight loss was the strongest negative predictor of delta-FIM (B = -9.094; P = 0.007). To conclude, nutritional status, mainly weight change, is an independent negative predictor for rehabilitation success.
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Evaluación Geriátrica/métodos , Fracturas de Cadera/rehabilitación , Evaluación Nutricional , Fracturas Osteoporóticas/rehabilitación , Pérdida de Peso , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Israel , Tiempo de Internación/estadística & datos numéricos , Masculino , Pruebas de Estado Mental y Demencia , Pronóstico , Recuperación de la Función/fisiología , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Background: The use of gastrostomy tubes for long-term nutritional support in older patients is frequent. Percutaneous gastrostomy tube placement may be performed using various techniques, including endoscopic, surgical, and radiologically-guided methods. While percutaneous endoscopic gastrostomy (PEG) placement is the most widely used and accepted approach, experience with the use of percutaneous radiological gastrostomy (PRG) is more limited. Objective: To evaluate the safety and short-term outcomes of PRG in older patients requiring long-term enteral feeding. Method: We performed a prospective study involving all patients aged 65 years and older who underwent PRG insertion at the Laniado hospital over a period of 2 years. Adverse events related to the gastrostomy tube insertion were recorded over a period of 3 months following the procedure. Results: A total of 58 patients were included with a mean age of 78.1 years, and 48% were women. The most frequent indications for enteral feeding were stroke (47%) and dementia (41%). The technical success rate was 100% with no immediate procedure-related mortality or morbidity. One-month mortality was 3%, and overall mortality at 3-month follow-up was 16%. Complications were reported in 39 (67%) of patients, with 17 (29%) experiencing more than 1 complication. While most complications (88%) were minor, major complications occurred in 19 (33%) of the patients. Peritonitis was the cause of death in 2 patients, and tube dislodgment occurred in 17 subjects. During the follow-up period 17 (29%) of patients were re-admitted to hospital, with the cause for re-hospitalization being unrelated to the PRG in half of the cases. Neither bleeding nor deep wound infection was detected in the study group. Conclusions: PRG is relatively safe and effective for gastrostomy placement in older patients, and this technique may be of value in patients with oral infections and those receiving anti-thrombotic therapy.
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Despite the high prevalence of traumatic brain injuries (TBI), there are few rapid and straightforward tests to improve its assessment. To this end, we developed a tablet-based software battery ("BrainCheck") for concussion detection that is well suited to sports, emergency department, and clinical settings. This article is a study of the diagnostic accuracy of BrainCheck. We administered BrainCheck to 30 TBI patients and 30 pain-matched controls at a hospital Emergency Department (ED), and 538 healthy individuals at 10 control test sites. We compared the results of the tablet-based assessment against physician diagnoses derived from brain scans, clinical examination, and the SCAT3 test, a traditional measure of TBI. We found consistent distributions of normative data and high test-retest reliability. Based on these assessments, we defined a composite score that distinguishes TBI from non-TBI individuals with high sensitivity (83%) and specificity (87%). We conclude that our testing application provides a rapid, portable testing method for TBI.
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Conmoción Encefálica/diagnóstico , Lesiones Traumáticas del Encéfalo/diagnóstico , Neuroimagen/métodos , Programas Informáticos , Adolescente , Adulto , Anciano , Traumatismos en Atletas/diagnóstico , Conmoción Encefálica/fisiopatología , Lesiones Traumáticas del Encéfalo/fisiopatología , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Neuronal computation involves the integration of synaptic inputs that are often distributed over expansive dendritic trees, suggesting the need for compensatory mechanisms that enable spatially disparate synapses to influence neuronal output. In hippocampal CA1 pyramidal neurons, such mechanisms have indeed been reported, which normalize either the ability of distributed synapses to drive action potential initiation in the axon or their ability to drive dendritic spiking locally. Here we report that these mechanisms can coexist, through an elegant combination of distance-dependent regulation of synapse number and synaptic expression of AMPA and NMDA receptors. Together, these complementary gradients allow individual dendrites in both the apical and basal dendritic trees of hippocampal neurons to operate as facile computational subunits capable of supporting both global integration in the soma/axon and local integration in the dendrite.
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Región CA1 Hipocampal/metabolismo , Dendritas/metabolismo , Receptores AMPA/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapsis/metabolismo , Animales , Región CA1 Hipocampal/fisiología , Región CA1 Hipocampal/ultraestructura , Dendritas/fisiología , Dendritas/ultraestructura , Potenciales Postsinápticos Excitadores/fisiología , Masculino , Potenciales de la Membrana/fisiología , Modelos Neurológicos , Células Piramidales/metabolismo , Células Piramidales/fisiología , Células Piramidales/ultraestructura , Ratas , Receptores AMPA/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , Sinapsis/ultraestructuraRESUMEN
Social transmission of information is vital for many group-living animals, allowing coordination of motion and effective response to complex environments. Revealing the interaction networks underlying information flow within these groups is a central challenge. Previous work has modeled interactions between individuals based directly on their relative spatial positions: each individual is considered to interact with all neighbors within a fixed distance (metric range), a fixed number of nearest neighbors (topological range), a 'shell' of near neighbors (Voronoi range), or some combination (Figure 1A). However, conclusive evidence to support these assumptions is lacking. Here, we employ a novel approach that considers individual movement decisions to be based explicitly on the sensory information available to the organism. In other words, we consider that while spatial relations do inform interactions between individuals, they do so indirectly, through individuals' detection of sensory cues. We reconstruct computationally the visual field of each individual throughout experiments designed to investigate information propagation within fish schools (golden shiners, Notemigonus crysoleucas). Explicitly considering visual sensing allows us to more accurately predict the propagation of behavioral change in these groups during leadership events. Furthermore, we find that structural properties of visual interaction networks differ markedly from those of metric and topological counterparts, suggesting that previous assumptions may not appropriately reflect information flow in animal groups.
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Conducta Animal , Visión Ocular , Animales , Peces/fisiologíaRESUMEN
The spontaneous emergence of pattern formation is ubiquitous in nature, often arising as a collective phenomenon from interactions among a large number of individual constituents or sub-systems. Understanding, and controlling, collective behavior is dependent on determining the low-level dynamical principles from which spatial and temporal patterns emerge; a key question is whether different group-level patterns result from all components of a system responding to the same external factor, individual components changing behavior but in a distributed self-organized way, or whether multiple collective states co-exist for the same individual behaviors. Using schooling fish (golden shiners, in groups of 30 to 300 fish) as a model system, we demonstrate that collective motion can be effectively mapped onto a set of order parameters describing the macroscopic group structure, revealing the existence of at least three dynamically-stable collective states; swarm, milling and polarized groups. Swarms are characterized by slow individual motion and a relatively dense, disordered structure. Increasing swim speed is associated with a transition to one of two locally-ordered states, milling or highly-mobile polarized groups. The stability of the discrete collective behaviors exhibited by a group depends on the number of group members. Transitions between states are influenced by both external (boundary-driven) and internal (changing motion of group members) factors. Whereas transitions between locally-disordered and locally-ordered group states are speed dependent, analysis of local and global properties of groups suggests that, congruent with theory, milling and polarized states co-exist in a bistable regime with transitions largely driven by perturbations. Our study allows us to relate theoretical and empirical understanding of animal group behavior and emphasizes dynamic changes in the structure of such groups.
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Conducta Animal/fisiología , Cyprinidae/fisiología , Modelos Biológicos , Natación/fisiología , Animales , Simulación por ComputadorRESUMEN
Determining individual-level interactions that govern highly coordinated motion in animal groups or cellular aggregates has been a long-standing challenge, central to understanding the mechanisms and evolution of collective behavior. Numerous models have been proposed, many of which display realistic-looking dynamics, but nonetheless rely on untested assumptions about how individuals integrate information to guide movement. Here we infer behavioral rules directly from experimental data. We begin by analyzing trajectories of golden shiners (Notemigonus crysoleucas) swimming in two-fish and three-fish shoals to map the mean effective forces as a function of fish positions and velocities. Speeding and turning responses are dynamically modulated and clearly delineated. Speed regulation is a dominant component of how fish interact, and changes in speed are transmitted to those both behind and ahead. Alignment emerges from attraction and repulsion, and fish tend to copy directional changes made by those ahead. We find no evidence for explicit matching of body orientation. By comparing data from two-fish and three-fish shoals, we challenge the standard assumption, ubiquitous in physics-inspired models of collective behavior, that individual motion results from averaging responses to each neighbor considered separately; three-body interactions make a substantial contribution to fish dynamics. However, pairwise interactions qualitatively capture the correct spatial interaction structure in small groups, and this structure persists in larger groups of 10 and 30 fish. The interactions revealed here may help account for the rapid changes in speed and direction that enable real animal groups to stay cohesive and amplify important social information.
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Conducta Animal/fisiología , Cyprinidae/fisiología , Peces/fisiología , Animales , Modelos Biológicos , Movimiento/fisiología , Conducta Social , Programas Informáticos , Natación , Factores de TiempoRESUMEN
Competing models have been proposed to explain how neurons integrate the thousands of inputs distributed throughout their dendritic trees. In a simple global integration model, inputs from all locations sum in the axon. In a two-stage integration model, inputs contribute directly to dendritic spikes, and outputs from multiple branches sum in the axon. These two models yield opposite predictions of how synapses at different dendritic locations should be scaled if they are to contribute equally to neuronal output. We used serial-section electron microscopy to reconstruct individual apical oblique dendritic branches of CA1 pyramidal neurons and observe a synapse distribution consistent with the two-stage integration model. Computational modeling suggests that the observed synapse distribution enhances the contribution of each dendritic branch to neuronal output.
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Dendritas/ultraestructura , Hipocampo/citología , Vías Nerviosas/ultraestructura , Neuronas/ultraestructura , Sinapsis/ultraestructura , Animales , Hipocampo/anatomía & histología , Humanos , Microscopía Electrónica , Modelos Neurológicos , Redes Neurales de la ComputaciónRESUMEN
Recent advances in single-neuron biophysics have enhanced our understanding of information processing on the cellular level, but how the detailed properties of individual neurons give rise to large-scale behavior remains unclear. Here, we present a model of the hippocampal network based on observed biophysical properties of hippocampal and entorhinal cortical neurons. We assembled our model to simulate spatial alternation, a task that requires memory of the previous path through the environment for correct selection of the current path to a reward site. The convergence of inputs from entorhinal cortex and hippocampal region CA3 onto CA1 pyramidal cells make them potentially important for integrating information about place and temporal context on the network level. Our model shows how place and temporal context information might be combined in CA1 pyramidal neurons to give rise to splitter cells, which fire selectively based on a combination of place and temporal context. The model leads to a number of experimentally testable predictions that may lead to a better understanding of the biophysical basis of information processing in the hippocampus.
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Potenciales de Acción/fisiología , Algoritmos , Hipocampo/fisiología , Modelos Neurológicos , Red Nerviosa/fisiología , Neuronas/fisiología , Transmisión Sináptica/fisiología , Animales , Simulación por Computador , RatasRESUMEN
The essential amino acid methionine is a substrate for the synthesis of S-adenosyl-methionine (SAM), that donates its methyl group to numerous methylation reactions, and from which polyamines and ethylene are generated. To study the regulatory role of methionine synthesis in tomato fruit ripening, which requires a sharp increase in ethylene production, we cloned a cDNA encoding cystathionine gamma-synthase (CGS) from tomato and analysed its mRNA and protein levels during tomato fruit ripening. CGS mRNA and protein levels peaked at the "turning" stage and declined as the fruit ripened. Notably, the tomato CGS mRNA level in both leaves and fruit was negatively affected by methionine feeding, a regulation that Arabidopsis, but not potato CGS mRNA is subject to. A positive correlation was found between elevated ethylene production and increased CGS mRNA levels during the ethylene burst of the climacteric ripening of tomato fruit. In addition, wounding of pericarp from tomato fruit at the mature green stage stimulated both ethylene production and CGS mRNA level. Application of exogenous methionine to pericarp of mature green fruit increased ethylene evolution, suggesting that soluble methionine may be a rate limiting metabolite for ethylene synthesis. Moreover, treatment of mature green tomato fruit with the ethylene-releasing reagent Ethephon caused an induction of CGS mRNA level, indicating that CGS gene expression is regulated by ethylene. Taken together, these results imply that in addition to recycling of the methionine moieties via the Yang pathway, operating during synthesis of ethylene, de novo synthesis of methionine may be required when high rates of ethylene production are induced.
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Liasas de Carbono-Oxígeno/fisiología , Etilenos/biosíntesis , Frutas/crecimiento & desarrollo , Metionina/biosíntesis , Proteínas de Plantas/fisiología , Solanum lycopersicum/crecimiento & desarrollo , Liasas de Carbono-Oxígeno/genética , Liasas de Carbono-Oxígeno/metabolismo , Clonación Molecular , ADN Complementario/análisis , Frutas/enzimología , Frutas/genética , Regulación de la Expresión Génica de las Plantas , Solanum lycopersicum/enzimología , Solanum lycopersicum/genética , Metionina/farmacología , Compuestos Organofosforados/farmacología , Hojas de la Planta/enzimología , Hojas de la Planta/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , ARN Mensajero/metabolismoRESUMEN
The ability of synapses throughout the dendritic tree to influence neuronal output is crucial for information processing in the brain. Synaptic potentials attenuate dramatically, however, as they propagate along dendrites toward the soma. To examine whether excitatory axospinous synapses on CA1 pyramidal neurons compensate for their distance from the soma to counteract such dendritic filtering, we evaluated axospinous synapse number and receptor expression in three progressively distal regions: proximal and distal stratum radiatum (SR), and stratum lacunosum-moleculare (SLM). We found that the proportion of perforated synapses increases as a function of distance from the soma and that their AMPAR, but not NMDAR, expression is highest in distal SR and lowest in SLM. Computational models of pyramidal neurons derived from these results suggest that they arise from the compartment-specific use of conductance scaling in SR and dendritic spikes in SLM to minimize the influence of distance on synaptic efficacy.
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Hipocampo/metabolismo , Células Piramidales/metabolismo , Receptores AMPA/metabolismo , Sinapsis/metabolismo , Transmisión Sináptica/fisiología , Animales , Polaridad Celular/fisiología , Forma de la Célula/fisiología , Cruzamientos Genéticos , Espinas Dendríticas/metabolismo , Espinas Dendríticas/ultraestructura , Potenciales Postsinápticos Excitadores/fisiología , Ácido Glutámico/metabolismo , Hipocampo/citología , Citometría de Imagen , Inmunohistoquímica , Masculino , Microscopía Electrónica de Transmisión , Vía Perforante/metabolismo , Vía Perforante/ultraestructura , Terminales Presinápticos/metabolismo , Terminales Presinápticos/ultraestructura , Células Piramidales/citología , Ratas , Ratas Endogámicas BN , Ratas Endogámicas F344 , Sinapsis/ultraestructuraRESUMEN
Biochemical studies have identified two proteins, RB47 and RB60, that are involved in the light-regulated translation of the psbA mRNA in the chloroplast of the unicellular alga Chlamydomonas reinhardtii. RB47, a member of the eukaryotic poly(A)-binding protein family, binds directly to the 5' untranslated region of the mRNA, whereas RB60, a protein disulfide isomerase (PDI), is thought to bind to RB47 and to modulate its activity via redox and phosphorylation events. Our present studies show that RB47 forms a single disulfide bridge that most probably involves Cys143 and Cys259. We found that RB60 reacts with high selectivity with the disulfide of RB47, suggesting that the redox states of these two redox partners are coupled. Kinetics analysis indicated that RB47 contains two fast reacting cysteines, of which at least one is sensitive to changes in pH conditions. The results support the notion that light controls the redox regulation of RB47 function via the coupling of RB47 and RB60 redox states, and suggest that light-induced changes in stromal pH might contribute to the regulation.
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Chlamydomonas reinhardtii/enzimología , Cloroplastos/enzimología , Disulfuros/metabolismo , Proteína Disulfuro Isomerasas/metabolismo , Proteínas de Unión al ARN/metabolismo , Animales , Cisteína/análisis , Disulfuros/química , Luz , Oxidación-Reducción , Fosforilación , Proteína Disulfuro Isomerasas/química , Mapeo de Interacción de Proteínas , ARN Mensajero/metabolismo , ARN de Planta/metabolismo , Proteínas de Unión al ARN/químicaRESUMEN
We performed simultaneous patch-electrode recordings from the soma and apical dendrite of CA1 pyramidal neurons in hippocampal slices, in order to determine the degree of voltage attenuation along CA1 dendrites. Fifty per cent attenuation of steady-state somatic voltage changes occurred at a distance of 238 microm from the soma in control and 409 microm after blocking the hyperpolarization-activated (H) conductance. The morphology of three neurons was reconstructed and used to generate computer models, which were adjusted to fit the somatic and dendritic voltage responses. These models identify several factors contributing to the voltage attenuation along CA1 dendrites, including high axial cytoplasmic resistivity, low membrane resistivity, and large H conductance. In most cells the resting membrane conductances, including the H conductances, were larger in the dendrites than the soma. Simulations suggest that synaptic potentials attenuate enormously as they propagate from the dendrite to the soma, with greater than 100-fold attenuation for synapses on many small, distal dendrites. A prediction of this powerful EPSP attenuation is that distal synaptic inputs are likely only to be effective in the presence of conductance scaling, dendritic excitability, or both.
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Dendritas/fisiología , Hipocampo/fisiología , Células Piramidales/fisiología , Animales , Potenciales Postsinápticos Excitadores/fisiología , Hipocampo/ultraestructura , Técnicas In Vitro , Masculino , Modelos Neurológicos , Conducción Nerviosa/fisiología , Técnicas de Placa-Clamp , Células Piramidales/ultraestructura , Ratas , Ratas Wistar , Transmisión SinápticaRESUMEN
The 3' cleavage and polyadenylation of mRNAs has been studied in detail in animals and yeast, but not in plants. Aimed at elucidating the regulation of mRNA 3' end formation in plants, three Arabidopsis cDNAs encoding homologues of the animal proteins CstF-64, CstF-77 and CstF-50 that form the cleavage stimulating factor of the polyadenylation machinery have been cloned. It is shown experimentally that the N-terminal domain of the Arabidopsis CstF-64 homologue binds the mRNA 3' non-coding region in an analogous manner to the animal protein. It is also shown that the Arabidopsis CstF-64 and CstF-77 homologues strongly interact with each other in a similar way to their animal counterparts. These results imply that these Arabidopsis homologues belong to the polyadenylation machinery of nuclear mRNAs.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Factor de Estimulación del Desdoblamiento/genética , Poliadenilación/genética , ARN Mensajero/genética , Animales , Factor de Estimulación del Desdoblamiento/metabolismo , Clonación Molecular , Datos de Secuencia Molecular , Unión Proteica , Mapeo de Interacción de Proteínas , ARN Mensajero/metabolismo , Factores de Escisión y Poliadenilación de ARNm/genética , Factores de Escisión y Poliadenilación de ARNm/metabolismoRESUMEN
The 5'-leader and 3'-tail of chloroplast mRNAs have been suggested to play a role in posttranscriptional regulation of expression of the message. The regulation is thought to be mediated, at least in part, by regulatory proteins that are encoded by the nuclear genome and targeted to the chloroplast where they interact with chloroplast mRNAs. Previous studies identified high affinity binding of the 5'-untranslated region (UTR) of the chloroplast psbA mRNA by Chlamydomonas reinhardtii proteins. Here we tested whether the 3'-UTR of psbA mRNA alone or linked in cis with the 5'-UTR of the mRNA affects the high affinity binding of the message in vitro. We did not detect high affinity binding that is unique to the 3'-UTR. However, we show that the cis-linked 3'-UTR increases the stability of the 5'-UTR binding complex. This effect could provide a means for translational discrimination against mRNAs that are incorrectly processed.