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PURPOSE OF REVIEW: Chronic liver disease is a major cause of morbidity and mortality amongst people living with HIV (PLWH). Emerging data suggests that gut microbial translocation may play a role in driving and modulating liver disease, a bi-directional relationship termed the gut-liver axis. While it is recognized that PLWH have a high degree of dysbiosis and gut microbial translocation, little is known about the gut-liver axis in PLWH. RECENT FINDINGS: Recent studies have shown that microbial translocation can directly lead to hepatic inflammation, and have linked gut microbial signatures, dysbiosis, and translocation to liver disease in PLWH. Additionally, multiple trials have explored interventions targeting the microbiome in PLWH. Emerging research supports the interaction between the gut microbiome and liver disease in PLWH. This offers new opportunities to expand our understanding of the pathophysiology of liver disease in this population, as well as to explore possible clinical interventions.
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Microbioma Gastrointestinal , Infecções por HIV , Microbiota , Humanos , Disbiose , Infecções por HIV/complicações , FígadoRESUMO
Optogenetics is a transformative technology based on light-sensitive microbial proteins, known as opsins, that enable precise modulation of neuronal activity with pulsed radiant energy. Optogenetics has been proposed as a means to improve auditory implant outcomes by reducing channel interaction and increasing electrode density, but the introduction of opsins into cochlear spiral ganglion neurons (SGNs) in vivo has been challenging. Here we test opsin delivery using a synthetically developed ancestral adeno-associated virus (AAV) vector called Anc80L65. Wild-type C57BL/6 mouse pups were injected via the round window of cochlea with Anc80L65 carrying opsin Chronos under the control of a CAG promoter. Following an incubation of 6-22 weeks, pulsed blue light was delivered to cochlear SGNs via a cochleosotomy approach and flexible optical fiber. Optically evoked auditory brainstem responses (oABRs) and multiunit activity in inferior colliculus (IC) were observed. Post-experiment cochlear histology demonstrated opsin expression in SGNs (mean = 74%), with an even distribution of opsin along the cochlear basal/apical gradient. This study is the first to describe robust SGN transduction, opsin expression, and optically evoked auditory electrophysiology in neonatal mice. Ultimately, this work may provide the basis for a new generation of cochlear implant based on light.
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Vetores Genéticos/administração & dosagem , Opsinas/genética , Optogenética/métodos , Gânglio Espiral da Cóclea/metabolismo , Animais , Animais Recém-Nascidos , Implantes Cocleares , Dependovirus/genética , Potenciais Evocados Auditivos do Tronco Encefálico , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Opsinas/metabolismo , Fibras Ópticas , Gânglio Espiral da Cóclea/fisiologiaRESUMO
We show that chemistry can be used to trigger a nanofaceting transition. In particular, the segregation of Ag to an asymmetric tilt grain boundary in Cu is investigated. Aberration-corrected electron microscopy reveals that annealing the bicrystal results in the formation of nanometer-sized facets composed of preferentially Ag-segregated symmetric Σ5{210} segments and Ag-depleted {230}/{100} asymmetric segments. Our observations oppose an anticipated trend to form coarse facets. Atomistic simulations confirm the nanofacet formation observed in the experiment and demonstrate a concurrent grain boundary phase transition induced by the anisotropic segregation of Ag.
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OBJECTIVE: Cochlear explantation for purely elective (e.g. psychological and emotional) reasons is not well studied. Herein, we aim to provide data and expert commentary about elective cochlear implant (CI) removal that may help to guide clinical decision-making and formulate guidelines related to CI explantation. DATA SOURCES: We address these objectives via three approaches: case report of a patient who desired elective CI removal; review of literature and expert discussion by surgeon, audiologist, bioethicist, CI user and member of Deaf community. REVIEW METHODS: A systematic review using three scientific online databases was performed. Included articles addressed the benefits and/or complications of cochlear implantation in young children, CI explantation with or without revision surgery and the ethical debate between the medical and Deaf communities on cochlear implantation and explantation. CONCLUSIONS: The medical and audiological perspectives identify a host of risks related to implant removal without reimplantation, including risk from surgery, general anaesthesia, cochlear ossification and poor audiometric outcomes. The member of the deaf community and bioethicist argue that physicians need to guide the principles of beneficence, non-maleficence and patient autonomy. Taken together, patient desires should be seen as paramount, if the patient is otherwise fit for surgery and well informed. IMPLICATIONS FOR PRACTICE: Similar to the case of device implantation, device explantation should be a multidisciplinary and collaborative decision with the patient and the family's desires at the centre. While every case is different, we offer a CI explantation discussion to assist in clinical decision-making, patient counselling and education.
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Tomada de Decisão Clínica/ética , Implante Coclear , Implantes Cocleares , Remoção de Dispositivo/ética , Procedimentos Cirúrgicos Eletivos/ética , Implante Coclear/psicologia , Remoção de Dispositivo/psicologia , Procedimentos Cirúrgicos Eletivos/psicologia , Humanos , Educação de Pacientes como Assunto , Autonomia PessoalRESUMO
Introduction: Men who assault their partners present deficits in the social skills necessary for adequate interpersonal interaction. Not all of them have the same difficulties, thus they do not constitute a homogeneous group. Various studies have proposed different typologies of abusers based on their sociodemographic characteristics, criminal history, intensity and extent of violent or psychopathological traits. The majority of these investigations have been conducted in community samples, prompting the question of their validity in samples of men convicted of gender violence. The aim of this study was to establish a typology of men convicted in Spain for a gender violences crimes. Methodology: A total of 365 men participated and were subdivided into three classes of abusers based on their childhood, family experiences with violence, criminal history, sexist attitudes and attitudes toward violence, intensity and type of violence, psychopathological state and attachment style. Results: Coinciding with the results found in other research, 30% of the participants were classified as generally violent. They engaged in severe forms of physical, psychological and sexual violence and were more likely to do so than the rest. Additionally, they are more likely to present psychopathological problems and an antisocial character. Twenty-one percent were classified as dysphoric/borderline. They are characterized by minor forms of psychological violence, borderline or depressive symptomatology and an anxious attachment style. The remaining 49% were classified as familial or normalized abusers. This group exhibits moderate attitudes toward violence and sexism, resulting in less psychological and physical aggression. They do not present psychopathological problems and are likely to present a secure attachment style. Discussion: It is argued that determining the psychological characteristics of each type of abuser would contribute to improving and adapting intervention protocols in Spain, leading to a significant improvement in the current issue of abuse.
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Background: Steatohepatitis is common in persons living with HIV and may be associated with gut microbial translocation (MT). However, few studies have evaluated the gut-liver axis in persons living with HIV. In the Women's Interagency HIV Study, we examined the associations of HIV and circulating biomarkers linked to MT and gut damage using the FibroScan-aspartate aminotransferase (FAST) score, a noninvasive surrogate for steatohepatitis with advanced fibrosis. Methods: Among 883 women with HIV and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut damage (kynurenine and tryptophan ratio, intestinal fatty acid-binding protein, soluble CD14, and soluble CD163) with a log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST. Results: HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in women with HIV than women without HIV (P < .001 for each). MT biomarkers mediated 13% to 32% of the association of HIV and FAST score. Conclusions: Biomarkers linked to MT and gut damage are associated with a higher FAST score and mediate the association of HIV with a higher FAST score. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis.
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The appearance of water stress episodes triggers leaf abscission and decreases Ilex paraguariensis yield. To explore the mechanisms that allow it to overcome dehydration, we investigated how the root gene expression varied between water-stressed and non-stressed plants and how the modulation of gene expression was linked to metabolite composition and physiological status. After water deprivation, 5160 differentially expressed transcripts were obtained through RNA-seq. The functional enrichment of induced transcripts revealed significant transcriptional remodelling of stress-related perception, signalling, transcription, and metabolism. Simultaneously, the induction of the enzyme 9-cis-expoxycarotenoid dioxygenase (NCED) transcripts reflected the central role of the hormone abscisic acid in this response. Consequently, the total content of amino acids and soluble sugars increased, and that of starch decreased. Likewise, osmotic adjustment and radical growth were significantly promoted to preserve cell membranes and water uptake. This study provides a valuable resource for future research to understand the molecular adaptation of I. paraguariensis plants under drought conditions and facilitates the exploration of drought-tolerant candidate genes.
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Objective The auditory brain stem implant (ABI) is a neuroprosthesis placed on the surface of the cochlear nucleus (CN) to provide hearing sensations in children and adults who are not candidates for cochlear implantation. Contemporary ABI arrays are stiff and do not conform to the curved brain stem surface. Recent advancements in microfabrication techniques have enabled the development of flexible surface arrays, but these have only been applied in animal models. Herein, we measure the surface curvature of the human CN and adjoining regions to assist in the design and placement of next-generation conformable clinical ABI arrays. Three-dimensional (3D) reconstructions from ultrahigh T1-weighted brain magnetic resonance imaging (MRI) sequences and histologic reconstructions based on postmortem adult human brain stem specimens were used. Design This is a retrospective review of radiologic data and postmortem histologic axial sections. Setting This is set at the tertiary referral center. Participants Data were acquired from healthy adults. Main Outcome Measures The main outcome measures are principal curvature values (Kmin and Kmax) and global radius of curvature. Results The CN was successfully extracted and rendered as a 3D surface in all cases. Significant curvatures of the CN in both histologic and radiographic reconstructions were found with global radius of curvature ranging from 2.08 to 8.5 mm. In addition, local curvature analysis revealed that the surface is highly complex. Conclusion Detailed rendering of the human CN is feasible using histology and 3D MRI reconstruction and highlights complex surface topography that is not recapitulated by contemporary stiff ABI arrays.
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OBJECTIVE: Otologic methicillin-resistant Staphylococcus aureus (MRSA) infection has historically been rare, but given the rise in community-acquired MRSA carriage and infection at other body sites, prevalence rates may be changing. The goal of this study was to determine the prevalence of MRSA in recent otologic cultures from patients with acute otitis externa (AOE). STUDY DESIGN: Retrospective review of an institutional microbiologic database. METHODS: A retrospective analysis was performed on serial culture isolates taken from the ear at a quaternary care hospital from January 2014 to April 2016. The causative pathogen and antibiotic sensitivity was determined by culture isolation and end point mean inhibitory concentration (MIC) testing. Medical records were reviewed to document patient characteristics, chronicity of infection, symptomatology, and previous treatments. RESULTS: Over the study period, 173 patients were diagnosed with AOE and underwent otologic cultures of the ear. Fifty-three (30.6%) of cultures grew S . aureus (SA). Of SA infections, 15 (28.3%) were identified as MRSA. MRSA patients were typically older than patients with methicillin-sensitive SA (MSSA) (mean age 46.7 ± 17.9 vs 29 ± 19.4, P = 0.003) and had more medical comorbidities (4 vs 1.7, P = 0.001). Compared to patients with MSSA, patients with MRSA were significantly more likely to have had prior ototopical antibiotic exposure (37% vs 73%, P = 0.019). CONCLUSION: Contemporary ear culture isolates at quaternary care center show higher rates of MRSA compared to historical reports in the literature. Clinicians should consider ear cultures to identify MRSA AOE. LEVEL OF EVIDENCE: IV.
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OBJECTIVE: Otogenic brain abscesses are one of the most significant life-threatening complications of otologic infections. Given their low prevalence, otogenic brain abscesses require a high index of suspicion for diagnosis. In this systematic review, we aim to provide an analysis of otogenic brain abscesses and describe common clinical signs and symptoms, bacteriology, location, treatment options, morbidity, and mortality. DATA SOURCES: PubMed, Cochrane CENTRAL database, Google Scholar, and Scopus. METHODS: A systematic review of literature was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations. Variables assessed included clinical signs and symptoms, bacteriology, location, treatment, morbidity, and mortality. RESULTS: Twenty-nine studies met inclusion and exclusion criteria, corresponding to a total of 1307 otogenic abscess cases for review. Fifty-five percent of abscesses were found in the temporal lobe and 28% in the cerebellum. Most patients (88.3%) had a history of suppurative chronic otitis media. The most common symptoms were headache, altered mental status, papilledema, and meningeal irritation. Fever, nausea, and vomiting affected about 40% of patients. The most commonly cultured bacterial species was Proteus mirabilis. In addition to antibiotics, most otogenic brain abscesses were treated by burr hole aspiration. Average mortality following advent of computed tomography was 8.11%. CONCLUSION: Although rare, otogenic brain abscesses may occur as a complication of suppurative otitis media and require a high index of suspicion. Appropriate imaging studies and multidisciplinary expertise are crucial in the diagnosis and management. LEVEL OF EVIDENCE: 4.
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OBJECTIVE: Evaluate the relationship between objective audiometric and vestibular tests and patient symptoms in superior canal dehiscence (SCD) syndrome. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care center. PATIENTS: Ninety-eight patients with SCD, preoperative threshold audiograms, cervical vestibular evoked myogenic potential (cVEMP) thresholds, and computed tomography (CT) imaging were included. Clinical reports were reviewed for self-reported SCD symptoms. Twenty-five patients completed the Hearing Handicap Inventory (HHI), Dizziness Handicap Inventory (DHI), Autophony Index (AI), and the 36-item Short Form Survey (SF-36). MAIN OUTCOME MEASURES: Correlations between preoperative low-frequency air-bone gap (ABG), cVEMP thresholds, and symptoms (including HHI, DHI, AI, and SF-36). Symptoms included hearing loss, aural fullness, autophony, hyperacusis, tinnitus, vertigo, imbalance and sound-, pressure and exercise provoked dizziness. Secondary outcome measure: Correlations between changes of objective and subjective measures before and after surgery. RESULTS: Patients who reported hearing loss had larger ABGs at 250âHz than patients without subjective hearing loss (pâ=â0.001). ABGs and cVEMP thresholds did not correlate with any other symptom. No significant correlation was found between ABG or cVEMP threshold and the HHI, DHI, AI or Health Utility Value (derived from the SF-36 quality of life score). Following SCD surgery, ABG decreased (pâ<â0.001), cVEMP thresholds increased (pâ<â0.001) and overall symptoms, handicap scores and quality-of-life improved; however, there was no significant relationship between these measures. CONCLUSION: While threshold audiometry and cVEMP are important tools to diagnose SCD and monitor surgical outcomes, these measures showed no significant correlation with vestibular and most auditory symptoms or their severity.
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Audiometria , Doenças do Labirinto/complicações , Doenças do Labirinto/diagnóstico , Potenciais Evocados Miogênicos Vestibulares , Adulto , Idoso , Audiometria/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Canais Semicirculares/patologia , Potenciais Evocados Miogênicos Vestibulares/fisiologiaRESUMO
OBJECTIVE: To develop a novel approach combining low-frequency air-bone gap (ABG) and cervical vestibular evoked myogenic potential (cVEMP) thresholds to improve screening for superior canal dehiscence (SCD) syndrome. STUDY DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENTS: One hundred forty patients with SCD and 21 healthy age-matched controls were included. Ears for each patient were divided into three groups based on computed tomography (CT) findings: 1) dehiscent, 2) thin, or 3) unaffected. MAIN OUTCOME MEASURES: cVEMP and audiometric thresholds were analyzed and differences among groups were evaluated. RESULTS: We define the third window indicator (TWI) as the cVEMP thresholds at 500, 750, and 1000âHz adjusted for the ABG at 250âHz (i.e., subtracting ABG from cVEMP threshold). The TWI differentiates between dehiscent and nondehiscent control ears with a sensitivity of 82% and specificity of 100%, corresponding to a positive predictive value of 100%. ABGs and cVEMP thresholds were similar for healthy controls and patients with thin bone over the superior canal. CONCLUSION: This is the largest study to date examining the usefulness of cVEMPs in the diagnosis of SCD. Our "third window indicator" (TWI) combines cVEMP thresholds with the ABG at 250âHz to improve the ability to screen patients with SCD symptoms.
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Doenças do Labirinto/diagnóstico , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Adolescente , Adulto , Idoso , Audiometria/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Canais Semicirculares/patologia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Os autores procuraram fazer um estudo da utilização da técnica da mão sobre a boca em crianças, entrevistando 49 clínicos odontopediatras com no mínimo 5 anos de experiência e obtiveram respostas as quais permitiram um estudo e discussão sobre o assunto. Neste trabalho também foi incluído a experiência dos autores e dados obtidos em volumoso levantamento bibliográfico sobre o assunto. Após todos estes dados várias conclusões foram tiradas as quais podem servir de orientação de conduta quando da perspectiva do uso desta técnica