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Tuberculosis (TB) is a heterogenous disease in humans with individuals exhibiting a wide range of susceptibility. This heterogeneity is not captured by standard laboratory mouse lines. We used a new collection of 19 wild-derived inbred mouse lines collected from diverse geographic sites to identify novel phenotypes during Mycobacterium tuberculosis ( Mtb ) infection. Wild derived mice have heterogenous immune responses to infection that result in differential ability to control disease at early timepoints. Correlation analysis with multiple parameters including sex, weight, and cellular immune responses in the lungs revealed that enhanced control of infection is associated with increased numbers of CD4 T cells, CD8 T cells and B cells. Surprisingly, we did not observe strong correlations between IFN-γ production and control of infection. Although in most lines high neutrophils were associated with susceptibility, we identified a mouse line that harbors high neutrophils numbers yet controls infection. Using single-cell RNA sequencing, we identified a novel neutrophil signature associated with failure to control infection.
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Introduction: Although schizophrenia is associated with a broad range of symptoms including hallucinations, delusions, and reduced motivation, measures of cognitive dysfunction, including cognitive flexibility and executive function, are the strongest predictors of functional outcomes. Antipsychotic medications are useful for reducing psychotic symptoms, but they are ineffective at improving cognitive deficits. Despite extensive investment by industry, the transition from preclinical to clinical trials has not been successful for developing precognitive medications for individuals with schizophrenia. Here, we describe the optimisation of a novel dynamic strategy shifting task (DSST) using standard operant chambers to investigate the optimal stimuli required to limit the extensive training times required in previous tasks. Methods: We determined that optimal learning by male and female Sprague Dawley rats for the flexibility task incorporated dynamic strategy shifts between spatial rules, such as following a visual cue or responding at one location, and non-spatial rules, such as responding to a central visual or auditory cue. A minimum of 6 correct consecutive responses were required to make a within-session change in the behavioural strategies. As a proof of concept, we trained and tested 84 Sprague Dawley rats on the DSST, and then assessed their cognitive flexibility using a within-subject design after an acute dose of ketamine (0, 3, 10 mg/kg). Rats made fewer premature and more perseverant responses to initiate a trial following ketamine. The effects of ketamine on trials to criterion was dependent on the rule. Results: Ketamine induced a significant improvement on the reversal of a non-spatial visual discrimination rule. There was no significant effect of ketamine on the spatial visual or response discrimination rules. Discussion: The DSST is a novel assay for studying distinct forms of cognitive flexibility and offers a rapid and adaptable means of assessing the ability to shift between increasingly challenging rule conditions. The DSST has potential utility in advancing our understanding of cognitive processes and the underlying neurobiological mechanisms related to flexibility in neuropsychiatric and neurological conditions where executive dysfunctions occur.>.
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Excitotoxicity-induced cell death in motor neurons is a major therapeutic target for amyotrophic lateral sclerosis (ALS). Yan et al.1 present a novel compound to specifically disrupt extra-synaptic NMDAR complexes, extending the lifespan of the SOD1G93A ALS mouse and ameliorating cell death.
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Esclerosis Amiotrófica Lateral , Animales , Ratones , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/metabolismo , Ratones Transgénicos , Neuronas Motoras/metabolismo , Superóxido Dismutasa/metabolismo , Modelos Animales de EnfermedadRESUMEN
Boron monoxide (BO), prepared by the thermal condensation of tetrahydroxydiboron, was first reported in 1955; however, its structure could not be determined. With the recent attention on boron-based two-dimensional materials, such as borophene and hexagonal boron nitride, there is renewed interest in BO. A large number of stable BO structures have been computationally identified, but none are supported by experiments. The consensus is that the material likely forms a boroxine-based two-dimensional material. Herein, we apply advanced 11B NMR experiments to determine the relative orientations of B(B)O2 centers in BO. We find that the material is composed of D2h-symmetric O2B-BO2 units that organize to form larger B4O2 rings. Further, powder diffraction experiments additionally reveal that these units organize to form two-dimensional layers with a random stacking pattern. This observation is in agreement with earlier density functional theory (DFT) studies that showed B4O2-based structures to be the most stable.
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Tight control of the transcription process is essential for the correct spatial and temporal gene expression pattern during development and in homeostasis. Enhancers are at the core of correct transcriptional activation. The original definition of an enhancer is straightforward: a DNA sequence that activates transcription independent of orientation and direction. Dissection of numerous enhancer loci has shown that many enhancer-like elements might not conform to the original definition, suggesting that enhancers and enhancer-like elements might use multiple different mechanisms to contribute to transcriptional activation. Here, we review methodologies to identify enhancers and enhancer-like elements and discuss pitfalls and consequences for our understanding of transcriptional regulation.
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Elementos de Facilitación Genéticos , Transcripción Genética , Transcripción Genética/genética , Elementos de Facilitación Genéticos/genética , Regulación de la Expresión Génica , Activación Transcripcional , Regiones Promotoras GenéticasRESUMEN
Spaceflight associated neuro-ocular syndrome (SANS) refers to a distinct constellation of ocular, neurological and neuroimaging findings observed in astronauts during and following long duration spaceflight. These ocular findings, to include optic disc oedema, posterior globe flattening, chorioretinal folds and hyperopic shifts, were first described by NASA in 2011. SANS is a potential risk to astronaut health and will likely require mitigation prior to planetary travel with prolonged exposures to microgravity. While the exact pathogenesis of SANS is not completely understood, several hypotheses have been proposed to explain this neuro-ocular phenomenon. In this paper, we briefly discuss the current hypotheses and contributing factors underlying SANS pathophysiology as well as analogues used to study SANS on Earth. We also review emerging potential countermeasures for SANS including lower body negative pressure, nutritional supplementation and translaminar pressure gradient modulation. Ongoing investigation within these fields will likely be instrumental in preparing and protecting astronaut vision for future spaceflight missions including deep space exploration.
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Papiledema , Vuelo Espacial , Ingravidez , Humanos , Papiledema/diagnóstico , Papiledema/etiología , Astronautas , Ingravidez/efectos adversosRESUMEN
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with heterogeneous aetiology and a complex genetic background. Effective therapies are therefore likely to act on convergent pathways such as dysregulated energy metabolism, linked to multiple neurodegenerative diseases including ALS. METHODS: Activity of the glycolysis enzyme phosphoglycerate kinase 1 (PGK1) was increased genetically or pharmacologically using terazosin in zebrafish, mouse and ESC-derived motor neuron models of ALS. Multiple disease phenotypes were assessed to determine the therapeutic potential of this approach, including axon growth and motor behaviour, survival and cell death following oxidative stress. FINDINGS: We have found that targeting a single bioenergetic protein, PGK1, modulates motor neuron vulnerability in vivo. In zebrafish models of ALS, overexpression of PGK1 rescued motor axon phenotypes and improved motor behaviour. Treatment with terazosin, an FDA-approved compound with a known non-canonical action of increasing PGK1 activity, also improved these phenotypes. Terazosin treatment extended survival, improved motor phenotypes and increased motor neuron number in Thy1-hTDP-43 mice. In ESC-derived motor neurons expressing TDP-43M337V, terazosin protected against oxidative stress-induced cell death and increased basal glycolysis rates, while rescuing stress granule assembly. INTERPRETATION: Our data demonstrate that terazosin protects motor neurons via multiple pathways, including upregulating glycolysis and rescuing stress granule formation. Repurposing terazosin therefore has the potential to increase the limited therapeutic options across all forms of ALS, irrespective of disease cause. FUNDING: This work was supported by project grant funding from MND Scotland, the My Name'5 Doddie Foundation, Medical Research Council Doctoral Student Training Fellowship [Ref: BST0010Z] and Academy of Medical Sciences grant [SGL023\1100].
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Esclerosis Amiotrófica Lateral , Fosfoglicerato Quinasa/metabolismo , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/metabolismo , Animales , Proteínas de Unión al ADN/genética , Humanos , Ratones , Neuronas Motoras/metabolismo , Fenotipo , Fosfoglicerato Quinasa/genética , Prazosina/análogos & derivados , Pez Cebra/metabolismoRESUMEN
In financial time series there are time periods in which market indices values or assets prices increase or decrease monotonically. We call those events "price runs", "elementary uninterrupted trends" or just "uninterrupted trends". In this paper we study the distribution of the duration of uninterrupted trends for the daily indices DJIA, NASDAQ, IPC and Nikkei 225 during the period of time from 10/30/1978 to 08/07/2020 and we compare the simple geometric statistical model with [Formula: see text] consistent with the EMH to the empirical data. By a fitting procedure, it is found that the geometric distribution with parameter [Formula: see text] provides a good model for uninterrupted trends of short and medium duration for the more mature markets; however, longest duration events still need to be statistically characterized. Estimated values of the parameter p were also obtained and confirmed by calculating the mean value of p fluctuations from empirical data. Additionally, the observed trend duration distributions for the different studied markets are compared over time by means of the Anderson-Darling (AD) test, to the expected geometric distribution with parameter [Formula: see text] and to a geometric distribution with a free parameter p, making possible to assess and compare different market geometric behavior for different dates as well as to measure the fraction of time runs duration from studied markets are consistent with the geometric distribution with [Formula: see text] and in parametric free way.
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Análisis de Datos , Distribuciones Estadísticas , Factores de TiempoRESUMEN
BACKGROUND & AIMS: Rifaximin-α is efficacious for the prevention of recurrent hepatic encephalopathy (HE), but its mechanism of action remains unclear. We postulated that rifaximin-α reduces gut microbiota-derived endotoxemia and systemic inflammation, a known driver of HE. METHODS: In a placebo-controlled, double-blind, mechanistic study, 38 patients with cirrhosis and HE were randomised 1:1 to receive either rifaximin-α (550 mg BID) or placebo for 90 days. PRIMARY OUTCOME: 50% reduction in neutrophil oxidative burst (OB) at 30 days. SECONDARY OUTCOMES: changes in psychometric hepatic encephalopathy score (PHES) and neurocognitive functioning, shotgun metagenomic sequencing of saliva and faeces, plasma and faecal metabolic profiling, whole blood bacterial DNA quantification, neutrophil toll-like receptor (TLR)-2/4/9 expression and plasma/faecal cytokine analysis. RESULTS: Patients were well-matched: median MELD (11 rifaximin-α vs. 10 placebo). Rifaximin-α did not lead to a 50% reduction in spontaneous neutrophil OB at 30 days compared to baseline (p = 0.48). However, HE grade normalised (p = 0.014) and PHES improved (p = 0.009) after 30 days on rifaximin-α. Rifaximin-α reduced circulating neutrophil TLR-4 expression on day 30 (p = 0.021) and plasma tumour necrosis factor-α (TNF-α) (p <0.001). Rifaximin-α suppressed oralisation of the gut, reducing levels of mucin-degrading sialidase-rich species, Streptococcus spp, Veillonella atypica and parvula, Akkermansia and Hungatella. Rifaximin-α promoted a TNF-α- and interleukin-17E-enriched intestinal microenvironment, augmenting antibacterial responses to invading pathobionts and promoting gut barrier repair. Those on rifaximin-α were less likely to develop infection (odds ratio 0.21; 95% CI 0.05-0.96). CONCLUSION: Rifaximin-α led to resolution of overt and covert HE, reduced the likelihood of infection, reduced oralisation of the gut and attenuated systemic inflammation. Rifaximin-α plays a role in gut barrier repair, which could be the mechanism by which it ameliorates bacterial translocation and systemic endotoxemia in cirrhosis. CLINICAL TRIAL NUMBER: ClinicalTrials.gov NCT02019784. LAY SUMMARY: In this clinical trial, we examined the underlying mechanism of action of an antibiotic called rifaximin-α which has been shown to be an effective treatment for a complication of chronic liver disease which effects the brain (termed encephalopathy). We show that rifaximin-α suppresses gut bacteria that translocate from the mouth to the intestine and cause the intestinal wall to become leaky by breaking down the protective mucus barrier. This suppression resolves encephalopathy and reduces inflammation in the blood, preventing the development of infection.
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Encefalopatía Hepática/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Mucinas/metabolismo , Rifaximina/farmacología , Adulto , Anciano , Método Doble Ciego , Femenino , Fármacos Gastrointestinales/metabolismo , Fármacos Gastrointestinales/farmacología , Fármacos Gastrointestinales/uso terapéutico , Encefalopatía Hepática/fisiopatología , Humanos , Inflamación/epidemiología , Inflamación/prevención & control , Cirrosis Hepática/epidemiología , Cirrosis Hepática/fisiopatología , Masculino , Persona de Mediana Edad , Mucinas/efectos de los fármacos , Ontario/epidemiología , Placebos , Rifaximina/metabolismo , Rifaximina/uso terapéuticoRESUMEN
Primary care physicians (PCPs) in Hawai'i face many challenges in treating patients with substance use disorders (SUD) who tend to have higher medical complexity and thus require more resources. PCPs play a vital role in identifying early misuse, integrating and coordinating care for patients with SUD including office-based interventions like medication-assisted treatment, and connecting patients to community treatment programs. In addition to enormous burdens to care for and increasingly complex patient panels, the challenges include lack of education on addiction medicine, insufficient resources and SUD treatment programs in the office and community, low reimbursement for the complexity of care provided, and an overall physician shortage which drives higher patient volume and less time for any given physician. This article suggests responses to address these challenges such as providing more training and continuing education in SUD for PCPs and trainees, enhancing team-based care to better support PCPs, and funding more SUD treatment programs. More funding should widen accessibility to treatment and reduce the overall burden on the health care system by preventing or treating the disease early, which is a core principle of primary care. Additionally, incentives to practice in Hawai'i in primary care, and especially to treat patients with SUD, need to be improved. Such steps must be taken to address the overall physician shortage that limits patients' access to SUD treatment. A collaborative care model between PCPs, care managers, and addiction specialists is an example of an integrated care system that may address many of these challenges in the short term. To truly improve care for all in Hawai'i, however, system wide interventions are essential to increase the incentive for PCPs to remain and practice in Hawai'i to take care of its unique population, including those dealing with SUD.
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Médicos , Humanos , Hawaii , Atención Primaria de SaludRESUMEN
In the mammalian embryo, epiblast cells must exit the naïve state and acquire formative pluripotency. This cell state transition is recapitulated by mouse embryonic stem cells (ESCs), which undergo pluripotency progression in defined conditions in vitro. However, our understanding of the molecular cascades and gene networks involved in the exit from naïve pluripotency remains fragmentary. Here, we employed a combination of genetic screens in haploid ESCs, CRISPR/Cas9 gene disruption, large-scale transcriptomics and computational systems biology to delineate the regulatory circuits governing naïve state exit. Transcriptome profiles for 73 ESC lines deficient for regulators of the exit from naïve pluripotency predominantly manifest delays on the trajectory from naïve to formative epiblast. We find that gene networks operative in ESCs are also active during transition from pre- to post-implantation epiblast in utero. We identified 496 naïve state-associated genes tightly connected to the in vivo epiblast state transition and largely conserved in primate embryos. Integrated analysis of mutant transcriptomes revealed funnelling of multiple gene activities into discrete regulatory modules. Finally, we delineate how intersections with signalling pathways direct this pivotal mammalian cell state transition.
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Diferenciación Celular , Redes Reguladoras de Genes , Células Madre Embrionarias de Ratones/metabolismo , Animales , Células Cultivadas , Regulación del Desarrollo de la Expresión Génica , Ratones , Células Madre Embrionarias de Ratones/citología , TranscriptomaRESUMEN
Many genes are regulated by multiple enhancers that often simultaneously activate their target gene. However, how individual enhancers collaborate to activate transcription is not well understood. Here, we dissect the functions and interdependencies of five enhancer elements that together activate Fgf5 expression during exit from naive murine pluripotency. Four intergenic elements form a super-enhancer, and most of the elements contribute to Fgf5 induction at distinct time points. A fifth, poised enhancer located in the first intron contributes to Fgf5 expression at every time point by amplifying overall Fgf5 expression levels. Despite low individual enhancer activity, together these elements strongly induce Fgf5 expression in a super-additive fashion that involves strong accumulation of RNA polymerase II at the intronic enhancer. Finally, we observe a strong anti-correlation between RNA polymerase II levels at enhancers and their distance to the closest promoter, and we identify candidate elements with properties similar to the intronic enhancer.
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Elementos de Facilitación Genéticos , Factor 5 de Crecimiento de Fibroblastos/genética , Regulación del Desarrollo de la Expresión Génica , Células Madre Embrionarias de Ratones/metabolismo , Regiones Promotoras Genéticas , ARN Polimerasa II/genética , Animales , Línea Celular , Núcleo Celular/genética , Núcleo Celular/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Exones , Factor 5 de Crecimiento de Fibroblastos/metabolismo , Técnicas de Inactivación de Genes , Genes Reporteros , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Histonas/genética , Histonas/metabolismo , Intrones , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Ratones , Células Madre Embrionarias de Ratones/citología , ARN Polimerasa II/metabolismo , Análisis de Secuencia de ARN , Transducción de Señal , Análisis de la Célula Individual , Transcripción Genética , Proteína Fluorescente RojaRESUMEN
Cirrhotic portal hypertension is characterised by development of the decompensating events of ascites, encephalopathy, portal hypertensive bleeding and hepatorenal syndrome, which arise in a setting of cirrhosis-associated immune dysfunction (CAID) and define morbidity and prognosis. CAID describes the dichotomous observations that systemic immune cells are primed and display an inflammatory phenotype, while failing to mount robust responses to pathogen challenge. Bacterial infections including spontaneous bacterial peritonitis are common complications of advanced chronic liver disease and can precipitate variceal haemorrhage, hepatorenal syndrome and acute-on-chronic liver failure; they frequently arise from gut-derived organisms and are closely linked with dysbiosis of the commensal intestinal microbiota in advanced chronic liver disease.Here, we review the links between cirrhotic dysbiosis, intestinal barrier dysfunction and deficits of host-microbiome compartmentalisation and mucosal immune homoeostasis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies targeted at restoring intestinal eubiosis, augmenting gut barrier function and ameliorating the mucosal and systemic immune deficits that characterise and define the course of decompensated cirrhosis.
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Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/inmunología , Inmunoterapia/métodos , Cirrosis Hepática/inmunología , Cirrosis Hepática/microbiología , Traslocación Bacteriana , Disbiosis/inmunología , Disbiosis/microbiología , Interacciones Huésped-Patógeno , Humanos , Inmunidad Mucosa , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiología , Permeabilidad , FenotipoRESUMEN
AIMS: To report the surgical outcome of patients with severe Scheuermann's kyphosis treated using a consistent technique and perioperative management. METHODS: We reviewed 88 consecutive patients with a severe Scheuermann's kyphosis who had undergone posterior spinal fusion with closing wedge osteotomies and hybrid instrumentation. There were 55 males and 33 females with a mean age of 15.9 years (12.0 to 24.7) at the time of surgery. We recorded their demographics, spinopelvic parameters, surgical correction, and perioperative data, and assessed the impact of surgical complications on outcome using the Scoliosis Research Society (SRS)-22 questionnaire. RESULTS: The mean follow-up was 8.4 years (2 to 14.9). There were 85 patients (96.6%) with a thoracic deformity. Posterior spinal fusion with closing-wedge osteotomies and hybrid instrumentation was used in 86 patients; two patients underwent combined anterior and posterior spinal fusion. The mean kyphosis was corrected from 94.5° to 47.5° (p < 0.001). Coronal and sagittal balance returned to normal. The rate of complications was 12.5%: there were no neurological deficits, implant failure, or revision surgery. SRS-22 scores improved from a mean 3.6 (1.3 to 4.1) to 4.6 (4.2 to 5.0) at two years (p < 0.001) with a high rate of patient satisfaction. Non-smokers and patients with lower preoperative SRS-22 scores showed greater improvement in their quality of life. Sagittal pelvic balance did not change after correction of the kyphosis and correlated with lumbar lordosis but not with thoracic or thoracolumbar kyphosis. CONCLUSION: Posterior spinal fusion using hybrid instrumentation, closing-wedge osteotomies, and iliac bone grafting achieves satisfactory correction of a severe kyphosis resulting in improvements in physical and mental health and a high degree of patient-reported satisfaction. Cite this article: Bone Joint J 2021;103-B(1):148-156.
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Enfermedad de Scheuermann/cirugía , Adolescente , Femenino , Humanos , Masculino , Osteotomía/métodos , Fusión Vertebral/métodos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The contribution of ribosome heterogeneity and ribosome-associated proteins to the molecular control of proteomes in health and disease remains unclear. Here, we demonstrate that survival motor neuron (SMN) protein-the loss of which causes the neuromuscular disease spinal muscular atrophy (SMA)-binds to ribosomes and that this interaction is tissue-dependent. SMN-primed ribosomes are preferentially positioned within the first five codons of a set of mRNAs that are enriched for translational enhancer sequences in the 5' untranslated region (UTR) and rare codons at the beginning of their coding sequence. These SMN-specific mRNAs are associated with neurogenesis, lipid metabolism, ubiquitination, chromatin regulation and translation. Loss of SMN induces ribosome depletion, especially at the beginning of the coding sequence of SMN-specific mRNAs, leading to impairment of proteins that are involved in motor neuron function and stability, including acetylcholinesterase. Thus, SMN plays a crucial role in the regulation of ribosome fluxes along mRNAs encoding proteins that are relevant to SMA pathogenesis.
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Neuronas Motoras/patología , Atrofia Muscular Espinal/patología , Biosíntesis de Proteínas , Proteoma/análisis , ARN Mensajero/metabolismo , Ribosomas/metabolismo , Proteína 1 para la Supervivencia de la Neurona Motora/metabolismo , Animales , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Ratones , Neuronas Motoras/metabolismo , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/metabolismo , ARN Mensajero/genética , Ribosomas/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genética , TranscriptomaRESUMEN
PURPOSE: Autonomic dysfunction is a known consequence of chronic and excessive alcohol consumption. The aim of this systematic review was to characterise this phenomenon, describe the frequency at which it occurs and to explore the best management strategies. METHODS: A systematic, computer-based search was conducted using the PubMed database. All studies identified by the search were evaluated independently by at least three authors. For inclusion, studies had to report human subjects consuming ethanol in excess. Case reports and non-original studies were excluded from this review. RESULTS: A total of 55 studies were included in this review. According to cardiovascular reflex tests, 16-73% of chronic alcohol abusers suffer from autonomic dysfunction. The most commonly occurring symptom is erectile dysfunction, whilst other features such as postural dizziness are rare. The most important risk factor for this condition is total lifetime dose of ethanol, although there is mixed evidence supporting the role of other risk factors. The only management strategy currently explored in the literature is abstinence, which appears to lead to significant improvement in autonomic investigations. CONCLUSION: Current literature includes studies of highly heterogeneous populations, consuming differing volumes of alcohol over variable periods of time and utilising a number of different autonomic test batteries and criteria to diagnose autonomic dysfunction. Therefore, further research using homogeneous methods for measuring autonomic dysfunction in the field is needed. Despite this limitation, our review demonstrated that autonomic dysfunction is very common among alcohol abusers.
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Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , Alcoholismo/epidemiología , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Consumo de Bebidas Alcohólicas/fisiopatología , Alcoholismo/diagnóstico , Alcoholismo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Disfunción Eréctil/diagnóstico , Disfunción Eréctil/epidemiología , Disfunción Eréctil/fisiopatología , Femenino , Humanos , Masculino , Disautonomías Primarias/diagnóstico , Disautonomías Primarias/epidemiología , Disautonomías Primarias/fisiopatologíaRESUMEN
BACKGROUND: The aim of this systematic review was to compare surgical and non-surgical management of Weber B ankle fractures. METHODS: A systematic computer-based search was conducted using the MEDLINE (via OvidSP), EMBASE (via OvidSP) and Central databases. Data were extracted regarding functional outcome, radiological union, range of motion (RoM), infection rate and quality of life (QoL). RESULTS: There were no significant differences identified between surgical and non-surgical management of Weber B fractures with respect to functional outcome. There is a higher rate of complication following surgical management, including infection, reoperation, thromboembolic events and death. With respect to QoL and ankle RoM, this review identified no differences between surgical and non-surgical management. CONCLUSIONS: There is a need for further published literature evaluating the most efficacious management as there is a poverty of high-level research available. Currently, the available literature does not overwhelmingly favour a particular approach to Weber B ankle fractures.
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Fracturas de Tobillo/cirugía , Articulación del Tobillo/cirugía , Fijación de Fractura/métodos , Fracturas de Tobillo/diagnóstico , Fracturas de Tobillo/fisiopatología , Articulación del Tobillo/diagnóstico por imagen , Humanos , Calidad de Vida , Radiografía , Rango del Movimiento Articular , Resultado del TratamientoRESUMEN
The distal motor fibers of the tibial and sural nerves are predominantly derived from the S1 root. We aimed to describe the electrophysiological relationship of these two nerves. Clinical, radiological and neurophysiological data of patients with mild, length-dependent, peripheral neuropathy (PN) and subjects without PN were retrospectively collected and analyzed. Eighty-eight individuals without PN and 24 patients with mild axonal PN who had no evidence of lumbosacral radiculopathy were included for analysis. Significant positive correlations were observed for the tibial CMAP and the sural SNAP for both controls and patients. Multivariate linear regression analyses showed that the predicted tibial CMAP can be calculated using the following equations: for male subjects without PN, tibial CMAP = 20.7 - 0.21 × age; for female subjects without PN, tibial CMAP = 23.3 - 0.21 × age and for patients with mild PN, tibial CMAP = 2.7 + sural SNAP. This study demonstrates the high correlation between the tibial CMAP and the sural SNAP in subjects without PN and patients with mild axonal peripheral neuropathy, and provides mathematical equations for the calculation of the predicted tibial CMAP for such individuals.