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Dominant mutations and mislocalization or aggregation of Fused in Sarcoma (FUS), an RNA-binding protein (RBP), cause neuronal degeneration in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD), two incurable neurological diseases. However, the function of FUS in neurons is not well understood. To uncover the impact of FUS in the neuronal transcriptome, we used high-throughput sequencing of immunoprecipitated and cross-linked RNA (HITS-CLIP) of FUS in human brains and mouse neurons differentiated from embryonic stem cells, coupled with RNA-seq and FUS knockdowns. We report conserved neuronal RNA targets and networks that are regulated by FUS. We find that FUS regulates splicing of genes coding for RBPs by binding to their highly conserved introns. Our findings have important implications for understanding the impact of FUS in neurodegenerative diseases and suggest that perturbations of FUS can impact the neuronal transcriptome via perturbations of RBP transcripts.
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Intrones , Neuronas/metabolismo , Proteínas de Unión al ARN/genética , Esclerosis Amiotrófica Lateral/metabolismo , Esclerosis Amiotrófica Lateral/patología , Animales , Secuencia de Bases , Secuencia Conservada , Degeneración Lobar Frontotemporal/metabolismo , Degeneración Lobar Frontotemporal/patología , Humanos , Ratones , Lóbulo Temporal/metabolismoRESUMEN
Background: In Latin America (LA), the prevalence of dementia is expected to triple to 150 million people by 2050. The 2020 Lancet Commission report identified several modifiable dementia risk factors, yet few social and environmental factors, most relevant to vulnerable regions of LA, were highlighted in this report. We sought to assess the epidemiology of neurocognitive disorders (NCD) in Puente Piedra, one of the most socially and economically vulnerable districts of Lima, the capital of Peru. Methodology: This was a cross-sectional door-to-door observational study that used two-stage household sampling. One young adult (30-59 years) and one older adult (>60 years) per household were enrolled. We collected demographic, clinical, and neurocognitive data. Addenbrooke's Cognitive Examination (young adults) and the RUDAS-PE (older adults) were used, classifying participants as cognitively normal, possible mild NCD, or possible major NCD. Results: We enrolled 247 participants (median age 46 years; 67% female). One-fourth had not completed secondary school and more than 50% completed only secondary school. Most participants were housewives (46%) and 21% did not have health insurance. The overall prevalence of possible NCD was 30% (25.6 and 41.8% among younger adults and older adults, respectively). Among younger adults, those ages 55-59 years more frequently had NCD (70%) compared to younger age ranges. Among older adults, only 3 subjects (4.5%) had major NCD. Conclusion: We found a high frequency of possible NCDs in a socially and economically vulnerable community in Lima, Peru, with younger adults showing levels of NCD higher than expected. Our findings support the need for health systems to incorporate cognitive screenings programs for NCD in younger ages. Future research on NCD would include younger populations, particularly in vulnerable communities.
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Demencia , Piedra , Adulto Joven , Humanos , Femenino , Anciano , Persona de Mediana Edad , Masculino , Perú/epidemiología , Estudios Transversales , Trastornos Neurocognitivos/epidemiología , Trastornos Neurocognitivos/diagnósticoRESUMEN
PURPOSE: We estimated the prevalence of fluoroquinolone resistant Escherichia coli in patients undergoing repeat transrectal ultrasound guided prostate needle biopsy and identified high risk groups. MATERIALS AND METHODS: From January 2009 to March 2010 rectal swabs of 136 men from 3 institutions undergoing transrectal ultrasound guided prostate needle biopsy were obtained. There were 33 men with no previous biopsy who served as the controls. Participants completed questionnaires and rectal swab culture was obtained just before performing the prostate biopsy. Selective media was used to specifically isolate fluoroquinolone resistant E. coli and sensitivities were obtained. The patients were contacted via telephone 7 days after the procedure for a followup questionnaire. RESULTS: A total of 30 patients had cultures positive for fluoroquinolone resistant bacteria for an overall rate of 22% (95% CI 15, 29). Patients with diabetes and Asian ethnicity had higher risks of resistant rectal flora colonization (OR 2.3 and 2.8, respectively). However, differences did not reach statistical significance (p = 0.09 and p = 0.08, respectively). Patients with no prior biopsy had a positive rate of 15% (5 of 33) compared to 24% (25 of 103) in those with 1 or more prior biopsies (OR 1.8, p = 0.27). Five patients (3.6%) had post-biopsy fever while only 1 of those patients had a positive rectal swab. CONCLUSIONS: Using selective media to isolate fluoroquinolone resistant E. coli from the rectum before transrectal ultrasound guided prostate biopsy, we isolated organisms in 22% of patients with a wide resistance pattern. This protocol may be used to provide information regarding targeted antibiotic prophylaxis before transrectal prostate biopsies.
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Escherichia coli/efectos de los fármacos , Fluoroquinolonas/farmacología , Próstata/patología , Adulto , Anciano , Biopsia con Aguja/métodos , Farmacorresistencia Bacteriana , Escherichia coli/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Próstata/diagnóstico por imagen , Ultrasonografía IntervencionalRESUMEN
PURPOSE: After radical prostatectomy continence is commonly defined as no pads except a security pad or 0 to 1 pad. We evaluated the association of pad status and urinary quality of life to determine whether security and 1 pad status differ from pad-free status to better define 0 pads as the post-prostatectomy standard. MATERIALS AND METHODS: A total of 500 consecutive men underwent robot assisted radical prostatectomy from October 2003 to July 2007. Data were collected prospectively and entered into an electronic database. Postoperatively men completed self-administered validated questionnaires including questions on 1) daily pad use (0, security, 1, or 2 or more), 2) urine leakage (daily, about once weekly, less than once weekly or not at all), 3) urinary control (none, frequent dribbling, occasional dribbling or total control), 4) American Urological Association symptom score and 5) urinary quality of life. RESULTS: Postoperatively men who indicated 0 pad use had a mean +/- SE symptom score of 5.8 +/- 0.3 and pleased quality of life (1.16 +/- 0.08). In contrast, men with a security pad and 1 pad had a symptom score of 7.6 +/- 0.7 and 9.2 +/- 0.6 but mixed quality of life (2.78 +/- 0.18 and 3.41 +/- 0.15, respectively, p <0.0005). CONCLUSIONS: Results show a significant decrease in quality of life between no pads (1.16 or pleased), a security pad and 0 or 1 pad (2.78 and 3.41 or mixed, respectively). Findings do not support defining continence with a security pad or 0 to 1 pad. Continence should be strictly defined as 0 pads.
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Prostatectomía/efectos adversos , Calidad de Vida , Encuestas y Cuestionarios , Incontinencia Urinaria/etiología , Adulto , Anciano , Anciano de 80 o más Años , Pañales para Adultos/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Neuromyelitis optica (NMO) is a rare demyelinating disorder affecting the spinal cord and optic nerves. Like multiple sclerosis (MS), it predominantly affects women during childbearing years. The impact of neuraxial anesthesia on the course of NMO is uncertain. There are no large studies available to draw definitive conclusions regarding the safety of neuraxial anesthesia in this population. A review of the current literature suggests that neuraxial anesthesia is unlikely to exacerbate neurologic symptoms in pregnant patients with NMO. However, given the rarity of this disease entity among patients requesting epidural labor analgesia, we recommend taking a cautious approach.
RESUMEN
Postdural puncture headache (PDPH) is a recognized complication of neuraxial anesthesia. This case report documents 1 patient who developed PDPH following epidural anesthesia for postoperative pain control. The patient declined conventional treatments, including an epidural blood patch and intravenous caffeine. This report documents successful use of adjunct acupuncture for the management of PDPH. Additional research on acupuncture as a potential adjunctive therapy for PDPH is needed, particularly for patients who are reluctant to receive more invasive treatments.
Dolor de cabeza posterior a la punción dural (CPPD) es una complicación reconocida de la anestesia neuroaxial. Este informe documenta casos de un paciente que desarrolló CPPD después de la anestesia epidural para el control del dolor postoperatorio. El paciente se negó tratamientos convencionales, incluyendo un parche hemático epidural y la cafeína intravenosa. Este informe documenta el uso exitoso de la acupuntura complemento para la gestión de la CPPD. Se necesita investigación adicional sobre la acupuntura como un potencial tratamiento adyuvante para la CPPD, sobre todo para los pacientes que se resisten a recibir tratamientos más invasivos.
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OBJECTIVES: To describe cancer inpatients' prior-year use of complementary and integrative health (CIH) therapies and interest in receiving CIH therapies while in the hospital. DESIGN: Observational, cross-sectional survey of prior-year use of 12 different CIH approaches and interest in receiving any of 7 CIH services in the hospital. SETTING: Surgical oncology ward of an academic medical center. PARTICIPANTS: 166 hospitalized oncology patients, with an average age of 54 years. RESULTS: The most commonly used CIH approach was vitamins/nutritional supplements (67%), followed by use of a special diet (42%) and manual therapies (39%). More than 40% of patients expressed interest in each of the therapies if it was offered during their hospital stay, and 95% of patients were interested in at least one. More than 75% expressed interest in nutritional counseling and in massage. CIH use and interest varied somewhat by demographic and clinical characteristics. CONCLUSION: Rates of CIH use among patients with cancer were high, as were their preferences to have these services available in the inpatient setting. Hospitals have the opportunity to provide patient-centered care by developing capacity to provide inpatient CIH services.
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Terapias Complementarias , Hospitalización , Medicina Integrativa , Masaje , Neoplasias/terapia , Terapia Nutricional , Atención Dirigida al Paciente , Centros Médicos Académicos , Adulto , Anciano , Terapias Complementarias/estadística & datos numéricos , Consejo , Estudios Transversales , Femenino , Encuestas de Atención de la Salud , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de SaludRESUMEN
BACKGROUND: Effective pain management among hospitalized patients is an important aspect of providing quality care and achieving optimal clinical outcomes and patient satisfaction. Common pharmacologic approaches for pain, though effective, have serious side effects and are not appropriate for all inpatients. Findings from randomized controlled trials (RCTs) support the efficacy of acupuncture for many symptoms relevant to inpatients including postoperative pain, cancer-related pain, nausea and vomiting, and withdrawal from narcotic use. However, the extent to which findings from RCTs translate to real-world implementation of acupuncture in typical hospital settings is unknown. METHODS/DESIGN: In partnership with the launch of a clinical program offering acupuncture services to inpatients at the University of California San Francisco's Mount Zion Hospital, we are conducting a pilot study using a hybrid effectiveness-implementation design to: (1) assess the effectiveness of acupuncture to manage pain and other symptoms and improve patient satisfaction; and (2) evaluate the barriers and facilitators to implementing an on-going acupuncture service for inpatients. During a two-month pre-randomization phase, we evaluated and adapted clinical scheduling and treatment protocols with acupuncturists and hospital providers and pretested study procedures including enrollment, consent, and data collection. During a six-month randomization phase, we used a two-tiered consent process in which inpatients were first consented into a study of symptom management, randomized to be offered acupuncture, and consented for acupuncture if they accepted. We are also conducting in-depth interviews and focus groups to assess evidence, context, and facilitators of key provider and hospital administration stakeholders. DISCUSSION: Effectiveness research in "real-world" practice settings is needed to inform clinical decision-making and guide implementation of evidence-based acupuncture practices. To successfully provide clinical acupuncture services and maintain a rigorous research design, practice-based trials of acupuncture require careful planning and attention to setting-specific, contextual factors. TRIAL REGISTRATION: This trial has been registered in ClinicalTrials.gov. The identifier is NCT01988194, registered on November 5, 2013.
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Terapia por Acupuntura , Protocolos Clínicos , Manejo del Dolor , Humanos , Pacientes Internos , Proyectos PilotoAsunto(s)
Anestesiología , Internado y Residencia , Médicos , Anestesiología/educación , Benchmarking , Frecuencia Cardíaca , Humanos , Proyectos PilotoRESUMEN
UNLABELLED: Efficacy of sanitizers in an overhead spray and brush roller system was examined for reducing Salmonella on unwaxed, mature green tomatoes. Surface inoculated tomatoes were treated in the overhead spray system for 5, 15, 30, and 60 s. A sodium hypochlorite (NaOCl) study tested NaOCl (25, 50, and 100 mg/L) against a water control. A sanitizer study examined NaOCl (100 mg/L), chlorine dioxide (ClO2; 5 mg/L), peroxyacetic acid (PAA; 80 mg/L), and water. The overhead spray system was also compared to a scale-model flume. All NaOCl concentrations were significantly more effective at removing Salmonella than water and achieved at least a 3-log10 CFU/mL reduction at different treatment times (P < 0.05). NaOCl (100 mg/L) achieved a 4 ± 1.8 log10 CFU/mL reduction at 15 s. In the sanitizer study, NaOCl, ClO2, and PAA achieved at least a 3-log10 CFU/mL reduction at 15 s and between 3.9 and 5.5 log10 CFU/mL reductions at 30 to 60 s. NaOCl (100 mg/L) in the overhead spray system significantly reduced more Salmonella than in the flume at 15 to 60 s. NaOCl flume treatment only reached a 1.3 ± 1.1 log10 CFU/mL reduction at 15 s. Results of this study demonstrate the ability of sanitizers in the laboratory model overhead spray system to reduce Salmonella on tomato surfaces. An overhead spray system could be implemented instead of flumes to achieve higher pathogen reduction with less water and sanitizer use, thereby lowering packing costs. PRACTICAL APPLICATION: The use of a non-recirculating, overhead spray brush roller system could offer a cost effective and efficacious way of washing tomatoes. The use large communal dump tanks in tomato processing has been suspected as a source of contamination in the tomato processing process. If effective, the brush roller system could augment or possible replace currently used dump tanks.
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Desinfectantes/farmacología , Conservación de Alimentos/métodos , Frutas/microbiología , Salmonella/efectos de los fármacos , Solanum lycopersicum/microbiología , Adhesión Bacteriana/efectos de los fármacos , Compuestos de Cloro/economía , Compuestos de Cloro/farmacología , Recuento de Colonia Microbiana , Ahorro de Costo , Desinfectantes/economía , Conservación de Alimentos/economía , Frutas/economía , Frutas/crecimiento & desarrollo , Solanum lycopersicum/economía , Concentración Osmolar , Óxidos/economía , Óxidos/farmacología , Ácido Peracético/economía , Ácido Peracético/farmacología , Salmonella/aislamiento & purificación , Intoxicación Alimentaria por Salmonella/prevención & control , Hipoclorito de Sodio/economía , Hipoclorito de Sodio/farmacología , Especificidad de la Especie , Propiedades de Superficie/efectos de los fármacos , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: After removal of the Foley catheter after robot-assisted radical prostatectomy (RARP), recovery of continence can take days to months. We sought to identify a simple means to predict time to recovery of postoperative continence. PATIENTS AND METHODS: Preoperative characteristics on 172 men who were undergoing RARP were entered into an electronic database. All men were queried via telephone and/or returned a 7-day log of pad use. Men without need for pads were excluded (n=41). At 4 to 7 days, responses were grouped as: one pad (n=55), two pads (n=35), or three or more pads (n=41). Patients returned self-addressed postcards noting the date of 0-pad urinary status. Univariate and multivariate analysis of variables were assessed for ability to predict time to continence. RESULTS: No preoperative factors, such as age, International Index of Erectile Function-5, prostate-specific antigen level, American Urological Association symptom score, body mass index, uroflowmetry, nerve-sparing status, estimated blood loss, or prostate weight, were found to predict time to continence. Pad use at 4 to 7 days, however, was highly correlated with median time to continence. The median time to continence for men using one pad was 35 days, two pads was 42 days, and for three or more pads was 73 days (P=0.0001). CONCLUSIONS: As has been previously reported, we found no reliable baseline factors that predicted postoperative time to 0-pad continence. We did find that determining pad usage at 4 to 7 days after catheter removal strongly predicted time to pad-free continence. This method is simpler then pad weights, predicts high- and low-risk men for delayed continence, and can be used for counseling/intervention.
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Prostatectomía/métodos , Robótica , Incontinencia Urinaria/cirugía , Humanos , Pañales para la Incontinencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: This is the third publication that updates clinical outcomes using a novel technique to apply locoregional hypothermia to the pelvis during robot-assisted radical prostatectomy (RARP) to reduce inflammatory injury. This report updates urinary and sexual clinical outcomes with a minimum of 1 year follow-up. PATIENTS AND METHODS: Regional pelvic cooling (<30 degrees C) [corrected] was achieved with a prototype endorectal cooling balloon (ECB) during the course ofRARP. All clinical data were entered prospectively into an electronic database for historic (cases 1-666) and hypothermic groups (115 pts). Urinary and sexual outcomes were obtained using self-administered validated questionnaires. Continence was defined as no pads, and potency was defined as two affirmative answers to "erections adequate for penetration" and "were the erections satisfactory." RESULTS: Six patients were excluded: three ECB malfunction, three previous radiation/surgery. Median time to zero pad use was 39 days vs 62 days (hypothermic vs controls, P = 0.0003). At 1 year, overall pad-free continence was 96.3% (105/109) vs controls of 86.6%, P < 0.001. Potency was evaluated in all men (40-78 years) with preoperative International Index of Erectile Function-5 scores of 22 to 25. At 3 months, potency results were unchanged between groups: 24% vs 23%. At 15 months, the potency rates were significantly better for the hypothermic group, 83% vs controls 66%, P = 0.045. No difference in oncologic outcome was noted with cooling. CONCLUSIONS: Using a prototype cooling balloon, hypothermic RARP significantly improved time to continence and overall continence. Hypothermia also resulted in a modest but statistically significant improvement in potency at 15 months. Once cooling parameters have been optimized, a randomized multicenter clinical trial will be needed for validation.
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Hipotermia Inducida , Prostatectomía/métodos , Robótica , Adulto , Anciano , Disfunción Eréctil/prevención & control , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Incontinencia Urinaria/prevención & controlRESUMEN
INTRODUCTION: Radical prostatectomy undoubtedly causes inflammatory damage to surrounding neuromuscular tissues (i.e., bladder, urethra, and nerves) that may contribute to urinary incontinence. We report the use of local hypothermia during robot-assisted laparoscopic prostatectomy to attenuate this injury. METHODS: Regional pelvic cooling was achieved using cold intracorporeal irrigation and an endorectal cooling balloon (ECB). In all, 115 men undergoing hypothermic robot-assisted laparoscopic radical prostatectomy (hRLP) (case #667-782) were prospectively compared with a historical cohort (case #1-666). Intracorporeal rectal and neurovascular bundle temperatures (T) and intrarectal temperatures were measured. Continence was defined as zero urinary pads. Kaplan-Meier analysis of time to zero pads and multivariate Cox proportional hazards regression was used. RESULTS: Hypothermia was achieved in 112/115 patients; 6 were excluded (3 ECB malfunction, 2 prior radiation, and 1 completion prostatectomy). Median endorectal T = 18.7 degrees C (range 9.1-29.5 degrees C). Mean intracorporeal T = 25.58 degrees C (ECB + irrigation, range 19.4-34.0 degrees C). Three and 12-month hRLP zero pad rates were 81% to 89% and 100% for initial and extended cooling groups versus 65% and 89% for controls. Return to continence was significantly faster for hRLP versus controls: median time to zero pad use was 39 days for hRLP versus 62 days for controls. Multivariate analysis adjusting for American Urological Association (AUA) symptom score, nerve-sparing surgery, learning curve, international index of erectile function-5, age, and prostate weight demonstrated a significantly faster return to continence (hazard ratio = 1.526; 95% CI 1.11, 2.09). Trends toward improved continence were observed with colder temperatures and older patients. CONCLUSIONS: Local hypothermia during prostatectomy resulted in a significant improvement in early postoperative zero pad continence rates. Longer and deeper cooling appears to be associated with improved continence, particularly among older patients.