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Astrocytes are multi-functional glial cells in the central nervous system that play critical roles in modulation of metabolism, extracellular ion and neurotransmitter levels, and synaptic plasticity. Astrocyte-derived signaling molecules mediate many of these modulatory functions of astrocytes, including vesicular release of ATP. In the present study, we used a unique genetic mouse model to investigate the functional significance of astrocytic exocytosis of ATP. Using primary cultured astrocytes, we show that loss of vesicular nucleotide transporter (Vnut), a primary transporter responsible for loading cytosolic ATP into the secretory vesicles, dramatically reduces ATP loading into secretory lysosomes and ATP release, without any change in the molecular machinery of exocytosis or total intracellular ATP content. Deletion of astrocytic Vnut in adult mice leads to increased anxiety, depressive-like behaviors, and decreased motivation for reward, especially in females, without significant impact on food intake, systemic glucose metabolism, cognition, or sociability. These behavioral alterations are associated with significant decreases in the basal extracellular dopamine levels in the nucleus accumbens. Likewise, ex vivo brain slices from these mice show a strong trend toward a reduction in evoked dopamine release in the nucleus accumbens. Mechanistically, the reduced dopamine signaling we observed is likely due to an increased expression of monoamine oxidases. Together, these data demonstrate a key modulatory role of astrocytic exocytosis of ATP in anxiety, depressive-like behavior, and motivation for reward, by regulating the mesolimbic dopamine circuitry.
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To facilitate inter-tissue communication and the exchange of proteins, lipoproteins, and metabolites with the circulation, hepatocytes have an intricate and efficient intracellular trafficking system regulated by small Rab GTPases. Here, we show that Rab30 is induced in the mouse liver by fasting, which is amplified in liver-specific carnitine palmitoyltransferase 2 knockout mice (Cpt2L-/-) lacking the ability to oxidize fatty acids, in a Pparα-dependent manner. Live-cell super-resolution imaging and in vivo proximity labeling demonstrates that Rab30-marked vesicles are highly dynamic and interact with proteins throughout the secretory pathway. Rab30 whole-body, liver-specific, and Rab30; Cpt2 liver-specific double knockout (DKO) mice are viable with intact Golgi ultrastructure, although Rab30 deficiency in DKO mice suppresses the serum dyslipidemia observed in Cpt2L-/- mice. Corresponding with decreased serum triglyceride and cholesterol levels, DKO mice exhibit decreased circulating but not hepatic ApoA4 protein, indicative of a trafficking defect. Together, these data suggest a role for Rab30 in the selective sorting of lipoproteins to influence hepatocyte and circulating triglyceride levels, particularly during times of excessive lipid burden.
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Carnitina O-Palmitoiltransferase , Jejum , Hepatócitos , Homeostase , Metabolismo dos Lipídeos , Fígado , Camundongos Knockout , Proteínas rab de Ligação ao GTP , Animais , Masculino , Camundongos , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/genética , Colesterol/metabolismo , Jejum/metabolismo , Complexo de Golgi/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab de Ligação ao GTP/genética , Triglicerídeos/metabolismo , Triglicerídeos/sangueRESUMO
Dissolved Oxygen (DO) in water enables marine life. Measuring the prevalence of DO in a body of water is an important part of sustainability efforts because low oxygen levels are a primary indicator of contamination and distress in bodies of water. Therefore, aquariums and aquaculture of all types are in need of near real-time dissolved oxygen monitoring and spend a lot of money on purchasing and maintaining DO meters that are either expensive, inefficient, or manually operated-in which case they also need to ensure that manual readings are taken frequently which is time consuming. Hence a cost-effective and sustainable automated Internet of Things (IoT) system for this task is necessary and long overdue. DOxy, is such an IoT system under research and development at Santa Clara University's Ethical, Pragmatic, and Intelligent Computing (EPIC) Laboratory which utilizes cost-effective, accessible, and sustainable Sensing Units (SUs) for measuring the dissolved oxygen levels present in bodies of water which send their readings to a web based cloud infrastructure for storage, analysis, and visualization. DOxy's SUs are equipped with a High-sensitivity Pulse Oximeter meant for measuring dissolved oxygen levels in human blood, not water. Hence a number of parallel readings of water samples were gathered by both the High-sensitivity Pulse Oximeter and a standard dissolved oxygen meter. Then, two approaches for relating the readings were investigated. In the first, various machine learning models were trained and tested to produce a dynamic mapping of sensor readings to actual DO values. In the second, curve-fitting models were used to produce a successful conversion formula usable in the DOxy SUs offline. Both proved successful in producing accurate results.
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Objective: Valid performance on preseason baseline neurocognitive testing is essential for accurate comparison between preseason and post-concussion test results. Immediate Post-Concussion and Cognitive Testing (ImPACT) is commonly used to measure baseline neurocognitive function in athletes. We examined the prevalence of invalid performance on ImPACT baseline testing and identified correlates of invalid performance. Method: The sample included 66,998 adolescents (ages 14-18, M = 15.51 years, SD = 1.22) who completed ImPACT baseline tests between 2009 and 2019. Invalid performance was determined by the embedded validity indicators (EVI). Associations between invalid performance, demographic characteristics, and health conditions were assessed using chi-square tests and odds ratios (ORs). Results: Overall, 7.2% of adolescents had baseline tests identified as invalid by one or more of the EVIs. Individual validity indicators classified between 0.5% and 3.7% tests as invalid. Higher frequencies of invalid scores were observed among youth with neurodevelopmental, academic, and medical conditions. Youth who reported having learning disabilities (n = 3126), receiving special education (n = 3563), or problems with attention-deficit/hyperactivity disorder (ADHD; n = 5104) obtained invalid baselines at frequencies of 16.4%, 16.0%, and 11.1%, respectively. Moreover, youth who reported receiving treatment for a substance use disorder (n = 311) or epilepsy (n = 718) obtained invalid baselines at frequencies of 17.0% and 11.1%, respectively. Conclusions: The base rate of invalid performance on ImPACT's EVIs was approximately 7%, consistent with prior research. Adolescents self-reporting neurodevelopmental conditions, academic difficulties, or a history of treatment for medical conditions obtained invalid baseline tests at higher frequencies. More research is needed to better understand invalid scores in youth with pre-existing conditions.
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Atletas , Testes Neuropsicológicos , Humanos , Adolescente , Masculino , Feminino , Atletas/estatística & dados numéricos , Testes Neuropsicológicos/normas , Testes Neuropsicológicos/estatística & dados numéricos , Prevalência , Traumatismos em Atletas/epidemiologia , Traumatismos em Atletas/diagnóstico , Concussão Encefálica/epidemiologia , Concussão Encefálica/diagnóstico , Estudantes/estatística & dados numéricos , Reprodutibilidade dos TestesRESUMO
Whether social determinants of health are associated with clinical outcome following concussion among adolescents is not well established. The present study examined whether neighborhood-level determinants are associated with clinical recovery time following concussion in adolescents. Participants included adolescent student athletes (n = 130; mean age = 16.6, standard deviation = 1.2; 60.8% boys, 39.2% girls) who attended one of nine selected high schools in Maine, USA. The Area of Deprivation Index (ADI), an indicator of neighborhood disadvantage was used to group high schools as either high or low in neighborhood disadvantage. Athletic trainers entered injury and recovery dates into an online surveillance application between September 2014 and January 2020. Chi-squared analyses and Kaplan-Meier survival analyses were used to compare the groups on two clinical outcomes: days to return to school and days to return to sports. Results of chi-squared tests did not reveal between-group differences in return to school at 21 or 28 days. However, groups differed in the percentage of adolescents who had returned to sports by 21 days (greater neighborhood disadvantage, 62.5%, lesser neighborhood disadvantage 82.0%, χ2 = 4.96, p = 0.03, odds ratio [OR] = 2.73, 95% confidence interval [CI], 1.11-6.74) and 28 days (greater neighborhood disadvantage, 78.6%, lesser neighborhood disadvantage 94.0%, χ2 = 5.18, p = 0.02, OR = 4.27, 95% CI, 1.13-16.16) following concussion. A larger proportion of adolescents attending schools located in areas of greater neighborhood disadvantage took more than 21 and 28 days to return to sports. These results indicate an association between a multi-faceted proxy indicator of neighborhood disadvantage and clinical outcome following concussion. Further research is needed to better characterize factors underlying group differences in time to return to sports and the interactions between neighborhood disadvantage and other correlates of clinical recovery following concussion.
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Traumatismos em Atletas , Concussão Encefálica , Esportes , Masculino , Feminino , Humanos , Adolescente , Traumatismos em Atletas/epidemiologia , Concussão Encefálica/epidemiologia , Atletas , Instituições Acadêmicas , Características da VizinhançaRESUMO
Sulfation and desulfation of steroids are opposing processes that regulate the activation, metabolism, excretion, and storage of steroids, which account for steroid homeostasis. Steroid sulfation and desulfation are catalyzed by cytosolic sulfotransferase and steroid sulfatase, respectively. By modifying and regulating steroids, cytosolic sulfotransferase (SULT) and steroid sulfatase (STS) are also involved in the pathophysiology of steroid-related diseases, such as hormonal dysregulation, metabolic disease, and cancer. The estrogen sulfotransferase (EST, or SULT1E1) is a typical member of the steroid SULTs. This review is aimed to summarize the roles of SULT1E1 and STS in steroid homeostasis and steroid-related diseases.
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Doenças Metabólicas , Neoplasias , Humanos , Esteril-Sulfatase , Sulfotransferases/metabolismo , Esteroides , HomeostaseRESUMO
Multiple techniques have been developed in addition to pulmonary vein isolation (PVI) to improve the outcomes of catheter ablation in patients with persistent atrial fibrillation (AF). We sought to evaluate the long-term efficacy of alternative techniques used in our laboratory for the treatment of persistent AF, including spatiotemporal dispersion (SD) and low-voltage isolation (LVI). Consecutive patients with persistent AF who underwent catheter ablation with the studied techniques between July 2016 and December 2019 were included in the study. PVI alone was compared with PVI plus SD and PVI plus LVI in terms of long-term freedom from atrial tachycardia (AT) and AF recurrence. Follow-up data were obtained from clinical records and hospital visits, which included a 7-day Holter monitor and electrocardiograms. The study was approved by the institutional review board of Rhode Island Hospital. A total of 382 patients underwent catheter ablation at our institution during the study period. One hundred seventy-two patients had paroxysmal AF and were excluded from the study. The remaining 210 patients had persistent AF and were included in the study. One hundred and three patients underwent PVI alone, while 48 had the addition of LVI and 59 had SD. Additionally, freedom from AT/AF recurrence at 18 months was 68% in the group that underwent LVI, 49% in the SD group, and 40% in the group that underwent PVI alone (log-rank P = .014). Freedom from AF recurrence was 74% in the LVI group, 71% in the SD group, and 43% in the PVI-alone group (log-rank P = .002). On multivariate Cox regression, LVI and left atrial size were found to be independent predictors of recurrence (hazard ratio, 0.39; 95% confidence interval, 0.206-0.760; P = .005 and hazard ratio, 1.4; 95% confidence interval, 1.105-1.923; P = .008, respectively). LVI and SD in addition to PVI were associated with greater freedom from AT/AF recurrence at 18 months compared to PVI alone.
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OBJECTIVE: This study examines associations between lipoprotein(a) (Lp[a]), a low-density-like lipoprotein, and renal vein occlusion (RVO) in US cohorts to characterize its prognostic role in the setting of RVO. DESIGN: A two-phase retrospective cohort study. METHODS: In the first phase, patients with RVO and a Lp(a) quantitative laboratory value at a single tertiary centre were reviewed. Lp(a) status was assessed in association with age of RVO diagnosis, visual acuity, time to development of RVO, and central subfield thickness. In the second phase, the TriNetX US Collaborative Network, a large national database, also was queried for the presence of high or low Lp(a) values and diagnoses of RVO. RESULTS: The single tertiary care centre identified 45 patients with RVO and a laboratory value of Lp(a), finding no significant associations with respect to Lp(a) status and age of RVO onset, time from the laboratory draw to the development of RVO, visual acuity, and central subfield thickness (p > 0.05 for all). The TriNetX national database identified 35,687 patients with a high Lp(a) value (>30 mg/dL or 61 nmol/L) and 51,692 with a low Lp(a) value. An elevated Lp(a) value was not associated with higher odds of central (odds ratio [OR]â¯=â¯1.15; 95% CI, 0.88-1.50) or branch RVO (ORâ¯=â¯1.01; 95% CI, 0.76-1.36). CONCLUSION: Taken together, this analysis suggests a lack of association between Lp(a) value and risk of RVO. This study highlights the benefit of large national databases in the validation of laboratory value predictors identified through small-cohort observational studies.
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BACKGROUND AND OBJECTIVE: Little is known about factors affecting risk or time to development of fellow eye retinal vein occlusion (RVO). The purpose of this study was to examine the incidence and risk factors for fellow eye RVO. PATIENTS AND METHODS: This was a retrospective case-control study comparing unilateral and fellow eye RVO patients. This study was exempt by the Cleveland Clinic Institutional Review Board. RESULTS: Out of 1,083 patients, fellow eye RVO had a cumulative incidence of 3.6% (95% CI 2.61, 4.94) with a median time to development of 18 months (95% CI 6.0, 28.0). Fellow eye disease was associated with multiple characteristics including chronic kidney disease (odds ratio [OR] 3.78, 95% CI 1.89 to 7.55) and diabetic retinopathy (3.18, 1.57 to 6.44). CONCLUSION: While fellow eye RVO is relatively rare, it typically occurs within the first few years following initial diagnosis. Multiple characteristics were associated with fellow eye disease and time to onset. [Ophthalmic Surg Lasers Imaging Retina 2023;54:471-476.].
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Oclusão da Veia Retiniana , Humanos , Incidência , Estudos de Casos e Controles , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/epidemiologia , Oclusão da Veia Retiniana/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVE: Macular thickness fluctuations (MTF) over time may be more predictive of visual outcomes than absolute macular thickness in patients with diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (anti-VEGF). It is unclear whether this association exists in DME patients treated with intravitreal steroids or whether steroids confer reduced MTF versus anti-VEGF treatments. PATIENTS AND METHODS: MTF was compared before and after initiation of steroids in DME patients treated with intravitreal steroids. A mixed-effects linear regression model was used to determine the association between MTF and best-corrected visual acuity (BCVA). RESULTS: Mean 12-month MTF significantly decreased after steroid initiation (61.1 µm versus 53.5 µm, P = 0.04, n = 105 eyes). Mean BCVA after 12 months was not significantly different from baseline. No significant association between post-steroid MTF and 12-month BCVA was found. CONCLUSION: Steroid treatment decreases MTF while BCVA remains stable in DME patients previously treated with anti-VEGF. [Ophthalmic Surg Lasers Imaging Retina 2023;54:454-460.].
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Diabetes Mellitus , Retinopatia Diabética , Macula Lutea , Edema Macular , Humanos , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular , Esteroides/uso terapêutico , Injeções Intravítreas , Inibidores da Angiogênese/uso terapêutico , Resultado do Tratamento , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/tratamento farmacológicoRESUMO
PURPOSE: Saturday night retinopathy, the term coined by Jayam et al . in 1974, is a rare condition in which external compression of the orbit during a drug and alcohol stupor causes a unilateral orbitopathy with ophthalmoplegia and ischemic retinopathy. This condition has been increasingly reported in the last decade, correlating with an increasing burden of substance use. This condition mirrors a similar entity typically reported in patients following spinal surgery, where a headrest supporting the patient's face compresses the orbit. The current authors combine these 2 entities, entitled external compressive ischemic orbitopathy, and present a comprehensive literature review describing this entity. METHODS: A systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All related publications of vision loss in the setting of orbital compression were reviewed. Data collected included patient demographics, precipitating circumstances of vision loss, presenting ocular symptoms, outcomes, and ancillary imaging. RESULTS: In total 31 articles were selected for inclusion, yielding 46 patients. A total of 10 patients suffered orbitopathy in the setting of a drug stupor, and 36 following prone-positioned surgery. However, 79% of patients presented with visual acuity of light perception or worse. Also, 86% of patients presented with ophthalmoplegia, 92% with proptosis and orbital edema, and 86% with varying degrees of retinal ischemia. When compared with iatrogenic cases, self-induced stuporous cases demonstrated worse presenting visual acuity, ophthalmoplegia, retinal and choroidal filling, and worse final outcomes. CONCLUSION: External compressive ischemic orbitopathy is a severe vision-threatening condition that has been increasingly reported in the last decade.
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Exoftalmia , Oftalmopatia de Graves , Oftalmoplegia , Doenças Retinianas , Estupor , Humanos , Oftalmopatia de Graves/complicações , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/cirurgia , Estupor/complicações , Descompressão Cirúrgica/métodos , Órbita/cirurgia , Exoftalmia/etiologia , Transtornos da Visão/diagnóstico , Cegueira/complicações , Isquemia/complicações , Isquemia/cirurgiaRESUMO
Introduction: This systematic review examined whether race or ethnicity are associated with clinical outcomes (e.g., time to return to school/sports, symptom duration, vestibular deficits, and neurocognitive functioning) following sport-related concussion among child, adolescent, or college-aged student athletes. Additionally, this review assessed whether the existing literature on this topic incorporated or included broader coverage of social determinants of health. Methods: The online databases PubMed, MEDLINE®, PsycINFO®, CINAHL, Cochrane Library, EMBASE, SPORTDiscus, Scopus, and Web of Science were searched. Results: A total of 5,118 abstracts were screened and 12 studies met inclusion criteria, including 2,887 youth and young adults. Among the included articles, only 3 studies (25%) examined whether race and ethnicity were associated with outcomes following concussion as a primary objective. None of the studies assessed the association between social determinants of health and outcomes following concussion as a primary objective, although 5 studies (41.7%) addressed a social determinant of health or closely related topic as a secondary objective. Discussion: Overall, the literature to date is extremely limited and insufficient for drawing conclusions about whether race or ethnicity are categorically associated with outcomes from sport-related concussion, or more specifically, whether there are socioeconomic, structural, or cultural differences or disparities that might be associated with clinical outcome. Systematic review registration: identifier: PROSPERO, CRD42016041479, CRD42019128300.
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We conducted a content analysis of the literature underlying the Centers for Disease Control and Prevention (CDC) Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury Among Children (i.e., the "Guideline") to determine the extent to which social determinants of health (SDoH) were examined or addressed. The systematic review forming the basis for the Guideline included 37 studies addressing diagnosis, prognosis, and treatment/rehabilitation. We examined those studies to identify SDoH domains derived from the U.S. Department of Health and Human Services' Healthy People 2020 and 2030 websites. No study explicitly mentioned "social determinants of health," by name, and few studies addressed SDoH domains as a primary focus (ranging from 0% to 27% of studies across SDoH domains). The most frequently represented SDoH domains, described in an inferential or a descriptive manner, were Education Access and Quality (29.7% of studies), Social and Community Context (27.0% of studies), and Economic Stability (21.6% of studies). Health Care Access (13.5% of studies) was less well represented and no studies (0%) examined Neighborhood and Built Environment. In terms of the CDC clinical questions, SDoH were only examined as predictors of outcome (prognosis) and no studies examined SDoH in relation to diagnosis or treatment/rehabilitation. The Guideline includes some commentary on health literacy and socioeconomic status. Overall, social determinants of health are largely unrepresented as important or meaningful variables influencing the Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury Among Children, or in the studies that informed the Guideline.
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Concussão Encefálica , Equidade em Saúde , Determinantes Sociais da Saúde , Criança , Humanos , Concussão Encefálica/diagnóstico , Acessibilidade aos Serviços de Saúde , Prognóstico , Guias de Prática Clínica como Assunto , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: The rate of transvenous lead extraction (TLE) due to cardiac implantable electronic device (CIED) infection continues to rise. CIED infections are associated with significant morbidity and mortality. Temporary pacing in patients with active CIED infections after TLE can be challenging. Leadless pacing has emerged as an alternative approach in this patient population. OBJECTIVE: The purpose of this study was to describe the outcomes of a strategy using concomitant leadless pacemaker implantation and TLE in patients with active infections and ongoing pacing requirements. METHODS: This study involved all leadless pacemaker implantation procedures performed during TLE between June 2018 and September 2022 in the setting of active infection. Demographic characteristics, procedural details, and clinical outcomes were analyzed. RESULTS: The study included 86 patients with indications for ongoing pacing, 60 (70%) men with mean age 77.4 ± 10.5 years, who underwent TLE and concomitant leadless pacemaker implantation in the setting of active infection. There were no procedure-related complications. Sixty-five patients (76%) had evidence of bacteremia, 80% of whom were discharged to complete their antimicrobial treatment. During a median follow-up of 163 days (interquartile range 57-403 days), there were no recurrent infections. Of the 25 deaths (29%) during the study period, 22 (88%) were unrelated to the initial infection. Nine deceased patients (36%) had methicillin-resistant Staphylococcus aureus or Candida infections, 3 of whom had persistent infection despite TLE. CONCLUSION: Leadless pacing is a safe and efficacious approach for the management of patients with pacing requirements that undergo CIED extraction in the setting of active infection.
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Cardiopatias , Staphylococcus aureus Resistente à Meticilina , Marca-Passo Artificial , Infecções Relacionadas à Prótese , Masculino , Humanos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Resultado do Tratamento , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/terapia , Marca-Passo Artificial/efeitos adversos , Cardiopatias/complicações , Remoção de Dispositivo/métodosRESUMO
OBJECTIVE: To examine the time to onset of disease in the fellow eye of patients with unilateral DMO in routine clinical practice and to identify risk factors for development of bilateral DMO. DESIGN: Retrospective cohort study. PARTICIPANTS: One hundred forty treatment-naive patients 18 years or older with unilateral DMO presenting to Cole Eye Institute between January 2012 and July 2021. METHODS: Records of patients with unilateral DMO were reviewed for development of DMO in the fellow eye. Demographic, diabetic, ocular, and systemic characteristics were collected at initial DMO diagnosis date. Bivariate and multivariate analyses were performed and significant factors were modelled using Kaplan-Meier curves. RESULTS: Fifty patients with conversion to bilateral DMO and 90 patients without conversion were identified. Average time to bilateral DMO was 15.0 ± 15.7 months. 64% of patients converted within 1 year and 90% converted within 3 years. HbA1c (p = 0.003), diabetic retinopathy duration (p = 0.029), and diabetic foot disease (DFD) (p = 0.002) were identified as significant risk factors for conversion. Patients with better visual acuity at time of initial diagnosis and history of panretinal photocoagulation (PRP) (p = 0.044) or focal laser (p = 0.035) in the primary eye were also more likely to convert. CONCLUSIONS: Participants were most likely to develop fellow eye DMO within the first year after initial DMO diagnosis. In routine clinical practice, poor glycaemic control and DFD were risk factors associated with bilateral eye involvement. Clinicians may consider screening the fellow eye of high-risk individuals at each appointment within the first year of diagnosis.
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Diabetes Mellitus , Retinopatia Diabética , Edema Macular , Humanos , Edema Macular/diagnóstico , Edema Macular/etiologia , Retinopatia Diabética/complicações , Retinopatia Diabética/diagnóstico , Estudos Retrospectivos , Retina , Acuidade VisualRESUMO
Speech perception is known to be a multimodal process, relying not only on auditory input but also on the visual system and possibly on the motor system as well. To date there has been little work on the potential involvement of the somatosensory system in speech perception. In the present review, we identify the somatosensory system as another contributor to speech perception. First, we argue that evidence in favor of a motor contribution to speech perception can just as easily be interpreted as showing somatosensory involvement. Second, physiological and neuroanatomical evidence for auditory-somatosensory interactions across the auditory hierarchy indicates the availability of a neural infrastructure that supports somatosensory involvement in auditory processing in general. Third, there is accumulating evidence for somatosensory involvement in the context of speech specifically. In particular, tactile stimulation modifies speech perception, and speech auditory input elicits activity in somatosensory cortical areas. Moreover, speech sounds can be decoded from activity in somatosensory cortex; lesions to this region affect perception, and vowels can be identified based on somatic input alone. We suggest that the somatosensory involvement in speech perception derives from the somatosensory-auditory pairing that occurs during speech production and learning. By bringing together findings from a set of studies that have not been previously linked, the present article identifies the somatosensory system as a presently unrecognized contributor to speech perception.
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Percepção da Fala , Percepção da Fala/fisiologia , Fala/fisiologia , Fonética , Córtex Somatossensorial/fisiologia , Percepção Auditiva/fisiologia , Estimulação AcústicaRESUMO
BACKGROUND: Master athletes encompass a wide range of exercise enthusiasts. At the extreme, there is an increased risk of atrial fibrillation (AF). Therapies aimed at rate or rhythm control are often limited given unfavorable side effects. Although studies suggest an increase in left atrial (LA) fibrosis in this population, minimal electrophysiologic data exist regarding the LA voltage mapping and the efficacy of AF ablation with pulmonary vein isolation (PVI). METHODS: In a retrospective single-center study, we reviewed AF ablations (pulmonary vein isolation and assessment/ablation of non-pulmonary vein triggers) performed in extreme master athletes with AF. We define "extreme" as those who have repeatedly competed in long distance endurance events for a > 10-year period. Bipolar voltage mappings obtained through PENTARAY Catheter (Biosense Webster) were reviewed using CARTO. LA scarring was defined as an area of less than 0.1 mV. All patients were monitored as outpatients for AF recurrence. RESULTS: Between January 2018 and February 2022, 16 patients (11 marathon runners, four long distance cyclers, and one marathon swimmer) underwent AF ablations. All patients in the cohort were male with an average CHA2DS2-VASc score of 1.2 ± 0.8 and left atrial volume of 34.4 cc/m2 ± 9.9. A total of eight patients (50%) had persistent AF. One patient (6.3%) had LA scar on bipolar voltage mapping, whom also had a non-pulmonary vein trigger of AF. Bidirectional blocks of the four pulmonary veins were achieved by radiofrequency (RF) ablation in all patients. Freedom from documented recurrence of AF up to 24 months was 93.8%. One patient (6.3%) had recurrence of AF at 14 months and underwent successful cardioversion. CONCLUSION: In our series of extreme master athletes with AF, the incidence of LA scarring on bipolar voltage mapping was low and the recurrence of AF following PVI by RF ablation was minimal.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Masculino , Feminino , Estudos Retrospectivos , Cicatriz , Técnicas Eletrofisiológicas Cardíacas , Resultado do Tratamento , Veias Pulmonares/cirurgia , Ablação por Cateter/efeitos adversos , Atletas , RecidivaRESUMO
Purpose: Secreted protein, acidic and rich in cysteine (SPARC) elevates intraocular pressure (IOP), increases certain structural extracellular matrix (ECM) proteins in the juxtacanalicular trabecular meshwork (JCT), and decreases matrix metalloproteinase (MMP) protein levels in trabecular meshwork (TM) endothelial cells. We investigated SPARC as a potential target for lowering IOP. We hypothesized that suppressing SPARC will decrease IOP, decrease structural JCT ECM proteins, and alter the levels of MMPs and/or their inhibitors. Methods: A lentivirus containing short hairpin RNA of human SPARC suppressed SPARC in mouse eyes and perfused cadaveric human anterior segments with subsequent IOP measurements. Immunohistochemistry determined structural correlates. Human TM cell cultures were treated with SPARC suppressing lentivirus. Quantitative reverse transcriptase polymerase chain reaction (PCR), immunoblotting, and zymography determined total RNA, relative protein levels, and MMP enzymatic activity, respectively. Results: Suppressing SPARC decreased IOP in mouse eyes and perfused human anterior segments by approximately 20%. Histologically, this correlated to a decrease in collagen I, IV, and VI in both the mouse TM and human JCT regions; in the mouse, fibronectin was also decreased but not in the human. In TM cells, collagen I and IV, fibronectin, MMP-2, and tissue inhibitor of MMP-1 were decreased. Messenger RNA of the aforementioned genes was not changed. Plasminogen activator inhibitor 1 (PAI-1) was upregulated in vitro by quantitative PCR and immunoblotting. MMP-1 activity was reduced in vitro by zymography. Conclusions: Suppressing SPARC decreased IOP in mice and perfused cadaveric human anterior segments corresponding to qualitative structural changes in the JCT ECM, which do not appear to be the result of transcription regulation.
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Fibronectinas , Osteonectina/metabolismo , Malha Trabecular , Animais , Cadáver , Colágeno Tipo I/metabolismo , Células Endoteliais/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Humanos , Pressão Intraocular , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinases da Matriz/metabolismo , Camundongos , Osteonectina/genética , Malha Trabecular/metabolismoRESUMO
BACKGROUND: Six months into the COVID-19 pandemic, college campuses faced uncertainty regarding the likely prevalence and spread of disease, necessitating large-scale testing to help guide policy following re-entry. METHODS: A SARS-CoV-2 testing program combining pooled saliva sample surveillance leading to diagnosis and intervention surveyed over 112,000 samples from 18,029 students, staff and faculty, as part of integrative efforts to mitigate transmission at the Georgia Institute of Technology in Fall 2020. RESULTS: Cumulatively, we confirmed 1,508 individuals diagnostically, 62% of these through the surveillance program and the remainder through diagnostic tests of symptomatic individuals administered on or off campus. The total strategy, including intensification of testing given case clusters early in the semester, was associated with reduced transmission following rapid case increases upon entry in Fall semester in August 2020, again in early November 2020, and upon re-entry for Spring semester in January 2021. During the Fall semester daily asymptomatic test positivity initially peaked at 4.1% but fell below 0.5% by mid-semester, averaging 0.84% across the Fall semester, with similar levels of control in Spring 2021. CONCLUSIONS: Owing to broad adoption by the campus community, we estimate that the program protected higher risk staff and faculty while allowing some normalization of education and research activities.