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Animal behavior emerges from integration of many processes with different spatial and temporal scales. Dynamical behavioral patterns, including daily and ultradian rhythms and the dynamical microstructure of behavior (i.e., autocorrelations properties), can be differentially affected by external cues. Identifying these patterns is important for understanding how organisms adapt to their environment, yet unbiased methods to quantify dynamical changes over multiple temporal scales are lacking. Herein, we combine a wavelet approach with Detrended Fluctuation Analysis to identify behavioral patterns and evaluate changes over 42-days in mice subjected to different dietary restriction paradigms. We show that feeding restriction alters dynamical patterns: not only are daily rhythms modulated but also the presence, phase and/or strength of ~12h-rhythms, as well as the nature of autocorrelation properties of feed-intake and wheel running behaviors. These results highlight the underlying complexity of behavioral architecture and offer insights into the multi-scale impact of feeding habits on physiology.
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Ritmo Ultradiano , Ratones , Animales , Actividad Motora/fisiología , Conducta Animal/fisiología , Ingestión de Alimentos , AgriculturaRESUMEN
OBJECTIVE: This study sought to identify the optimal temperature for moderate hypothermic circulatory arrest in patients undergoing elective hemiarch replacement with antegrade brain perfusion. METHODS: The Society of Thoracic Surgeons adult cardiac surgery database was queried for elective hemiarch replacements using antegrade brain perfusion for aneurysmal disease (2014-2019). Generalized estimating equations and restricted cubic splines were used to determine the risk-adjusted relationships between temperature as a continuous variable and outcomes. RESULTS: Elective hemiarch replacement with antegrade brain perfusion occurred in 3898 patients at 374 centers with a median nadir temperature of 24.9°C (first quartile, third quartile = 22.0°C, 27.5°C) and median circulatory arrest time of 19 minutes (first quartile, third quartile = 14.0 minutes, 27.0 minutes). After adjustment for comorbidities, circulatory arrest time, and individual surgeon, patients cooled between 25 and 28°C had an early survival advantage compared with 24°C, whereas those cooled between 21 and 23°C had higher risks of mortality compared with 24°C. A nadir temperature of 27°C was associated with the lowest risk-adjusted odds of mortality (odds ratio, 0.62; 95% confidence interval, 0.42-0.91). A nadir temperature of 21°C had the highest risk of mortality (odds ratio, 1.4; 95% confidence interval, 1.13-1.73). Risk of experiencing a major morbidity was elevated in patients cooled between 21 and 23°C, with the highest risk occurring in patients cooled to 21°C (odds ratio, 1.12; 95% confidence interval, 1.01-1.24). CONCLUSIONS: For patients with aneurysmal disease undergoing elective hemiarch with antegrade brain perfusion, circulatory arrest with a nadir temperature of 27°C confers the greatest early survival benefit and smallest risk of postoperative morbidity.
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Aneurisma de la Aorta Torácica , Paro Cardíaco , Adulto , Humanos , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Temperatura , Resultado del Tratamiento , Estudios Retrospectivos , Perfusión/efectos adversos , EncéfaloRESUMEN
The Mi-gene is widely used in different tomato cultivars to resist several Meloidogyne spp. (root-kot nematode; RKN), including M. incognita, M. javanica, and M. arenaria. Tomato cultivars with the Mi-gene are widely used in fields. However, factors such as temperatures, high initial population densities, and gene dosage can interfere with the expression of this gene. In addition, the presence of virulent species of RKN can limit the usefulness of the gene. One of the virulent species is M. haplanaria, which was identified infecting RKN-resistant tomato in Florida in 2015. The objectives of this study were to determine the initial damage threshold of M. haplanaria on tomato under greenhouse conditions and to analyze the impact of temperature and genetic background on virulence in tomato cultivars. The results showed a preliminary damage threshold of three eggs and J2/cm3 of soil. In addition, it was observed that M. haplanaria has a shorter life cycle than the virulent M. enterolobii and can infect, reproduce, and damage homozygous or heterozygous RKN-resistant tomato plants. This research demonstrated that M. haplanaria should be considered highly virulent on RKN-resistant tomato and is an important threat to agriculture in Florida.
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STUDY DESIGN: Retrospective Database Study. OBJECTIVE: Investigate utilization of bone morphogenetic protein (BMP-2) between 2004 and 2014. SUMMARY OF BACKGROUND DATA: The utilization, particularly off-label utilization, of BMP-2 has been controversial and debated in the literature. Given the concerns regarding cancer and potential complications, the risk benefit profile of BMP must be weighed with each surgical case. The debate regarding the costs and potential side effects of BMP-2 compared with autologous iliac crest bone harvest has continued. METHODS: The National Inpatient Sample (NIS) database was queried for the use of BMP-2 (ICD-9-CM 84.52) between 2004 and 2014 across 44 states. The NIS database represents a 20% sample of discharges, weighted to provide national estimates. BMP-2 utilization rates in spine surgery fusion procedures were calculated as a fraction of the total number of thoracic, lumbar, and sacral spinal fusion surgeries performed each year. RESULTS: Between 2004 and 2014, BMP-2 was utilized in 927,275 spinal fusion surgeries. In 2004, BMP-2 was utilized in 28.3% of all cases (N=48,613). The relative use of BMP-2 in spine fusion surgeries peaked in 2008 at 47.0% (N=112,180). Since then, it has continued to steadily decline with an endpoint of 23.6% of cases in 2014 (N=60,863). CONCLUSIONS: Throughout the United States, the utilization of BMP-2 in thoracolumbar fusion surgeries increased from 28.3% to 47.0% between 2004 and 2008. However, from 2008 to 2014, the utilization of BMP-2 in thoracolumbar spine fusion surgeries decreased significantly from 47.0% to 23.4%. While this study provides information on the utilization of BMP-2 for the entire United States over an 11-year period, further research is needed to the determine the factors affecting these trends.
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Proteína Morfogenética Ósea 2 , Fusión Vertebral , Proteína Morfogenética Ósea 2/uso terapéutico , Humanos , Región Lumbosacra , Estudios Retrospectivos , Fusión Vertebral/métodos , Estados UnidosRESUMEN
Background: The Lancet Commission on Global Surgery (LCoGS) surgical indicators have given the surgical community metrics for objectively characterizing the disparity in access to surgical healthcare. However, aggregate national statistics lack sufficient specificity to inform strengthening plans at the community level. We performed a second-stage analysis of Colombian surgical system service delivery to inform the development of resource- and context-sensitive interventions to inform a revision of the Decennial Public Health Plan for access inequity resolution. Methods: Data from the year 2016 to inform total operative volume (TOV) and 30-day non-risk adjusted peri-operative mortality (POMR) were collected from the Colombian national health information system. TOV and POMR were sub-characterized by demographics, urgency, service line, disease pathology and facility location. Findings: In 2016, aggregate national mortality was 0·87%, while mortality attributable to elective and emergency surgery was 0·73% and 1·30%, respectively. The elderly experienced a 5·6-fold higher mortality, with 4·2% undergoing an operation within 30 days of dying. Individuals undergoing hepatobiliary, thoracic, cardiac, and neurosurgical operations experienced the highest mortality rates while obstetrics, general surgery, orthopaedics, and urology performed the largest procedure volume. Finally, analysis of operation and service line specific POMR reveals opportunities for improvement. Interpretation: This granular second-stage analysis provides actionable data which is fundamental to the development of resource and context-sensitive interventions to address gaps and inequities in surgical system service delivery. Furthermore, this analysis validates the modeling underlying development of the LCoGS indicators. These data will inform the assessment of implementation priorities and revision of the Colombian Decennial Public Health Plan. Funding: None.
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PURPOSE: Belize has one of the highest cervical cancer burdens among Latin American and Caribbean countries, despite the implementation of national policies to increase access to prevention and treatment services. This study evaluates the policies, infrastructure, and workforce of the cervical cancer management system in Belize to inform capacity building efforts. METHODS: In 2018, health facility assessments were conducted across all six districts of Belize at the national pathology facility and 12 public facilities identified as critical to cervical cancer control. Human and infrastructure resource availability and existing policies related to cervical cancer screening and treatment services were assessed through a structured instrument. RESULTS: The public cervical cancer screening workforce in Belize consists of 75 primary care nurses and physicians-one per 1,076 screening-eligible women, with 44% conducting rural outreach. All districts have at least one screening facility, but 50% perform screening services only once per week. Colposcopy and loop electrical excision procedures are available in three and four districts, respectively; radical hysterectomy and chemotherapy are available in two districts; and radiation therapy is unavailable. Of essential pathology equipment, 38.5% were present and functional, 23% were present but nonfunctional, and 38.5% were unavailable. Additionally, 35% of supplies were unavailable at the time of assessment, and 75% were unavailable at least once in the 12 months before assessment. CONCLUSION: Public-sector cervical cancer management services differ among districts of Belize, with tertiary service availability concentrated in the largest district. Screening, outreach, and pathology are limited mostly by resource availability. This study characterizes the current capacity of services in Belize and pinpoints health system components for future investment and capacity-building efforts.
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Neoplasias del Cuello Uterino , Belice , Colposcopía , Atención a la Salud , Detección Precoz del Cáncer , Femenino , Humanos , Embarazo , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
The COVID-19 global pandemic has presented new challenges to radiology educators and their learners. As a specialty that is accustomed to adapting to continual technologic innovation, as well as one with the capacity for remote work, radiology is uniquely positioned to meet these challenges by taking advantage of online remote educational strategies. This represents an opportunity to not only leverage new methods and technologies but also reexamine the most effective way to implement established ones. The authors review the benefits of taking a purposeful goal-oriented approach to these challenges, provide a corresponding qreview of the general categories of resources that are currently available, and explore educational strategies by using broad categories of software solutions. An invited commentary by Awan is available online. Online supplemental material is available for this article. ©RSNA, 2021.
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Educación a Distancia/métodos , Radiología/educación , Recursos Audiovisuales , Educación Médica/métodos , Humanos , EnseñanzaRESUMEN
OBJECTIVE: As perioperative care pathways are developed to improve recovery, there is a need to explore the impact of age. The aim of this study was to compare the impact of a urogynecology-specific enhanced recovery after surgery (ERAS) pathway on perioperative outcomes across 3 age categories: young, middle age, and elderly. METHODS: A retrospective cohort study was conducted assessing same-day discharge, opioid administration, pain scores, and complications differences across and within 3 age categories, young (<61 years), middle age (61-75 years), elderly (>75 years), before and after ERAS implementation. RESULTS: Among 98 (25.7%) young, 202 (52.9%) middle-aged, and 82 (21.5%) elderly women, distribution before and after ERAS implementation was similar. In each age category, we found a commensurate increase in same-day discharge and decrease in length of stay independent of age. Age was associated with a variable response to opioid administration after ERAS. In women who received opioids, we found there was a greater reduction in opioids in elderly. Young women received 22.5 mg more than middle-aged women, whereas elderly women received 24.3 mg less than middle-aged women (P < 0.0001, P < 0.0001) for a mean difference of 46.8 mg between the youngest and oldest group. We found no significant differences in postanesthesia care unit pain scores with ERAS implementation. Complications did not increase after ERAS implementation in any age group, although younger and elderly women were more likely to experience complications independent of ERAS. CONCLUSIONS: Elderly women had similar outcomes compared with their younger counterparts after implementation of an ERAS pathway. Further research is needed to assess whether our age-related observations are generalizable.
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Recuperación Mejorada Después de la Cirugía , Prolapso de Órgano Pélvico/cirugía , Factores de Edad , Anciano , Analgésicos Opioides/uso terapéutico , Estudios de Cohortes , Utilización de Medicamentos/estadística & datos numéricos , Femenino , Humanos , Tiempo de Internación , Persona de Mediana Edad , Dimensión del Dolor , Alta del Paciente , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
Some patients undergoing routine SPECT/CT and PET/CT examinations during the COVID-19 pandemic may incidentally reveal findings of COVID-19-associated pneumonia (C-19AP) on localizing CT. It is critical for nuclear medicine physicians to develop diagnostic skills for timely recognition of typical findings of C-19AP on a localizing CT. Furthermore, it is our responsibility to know the optimal practices for safely isolating and managing such patients while protecting the staff, other patients at the facility, family and/or friend accompanying the patients, and the public in general from risky exposure to COVID-19 sources. We offer several steps following an encounter suspicious of C-19AP.
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Infecciones por Coronavirus/diagnóstico por imagen , Pulmón/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Diagnóstico Diferencial , Manejo de la Enfermedad , Humanos , Hallazgos Incidentales , Pandemias , Neumonía/etiología , Neumonía/terapia , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/terapia , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/normas , Columna Vertebral/diagnóstico por imagenRESUMEN
BACKGROUND: Surgical, anaesthetic, and obstetric (SAO) health-care system strengthening is needed to address the emergency and essential surgical care that approximately 5 billion individuals lack globally. To our knowledge, a complete, non-modelled national situational analysis based on the Lancet Commission on Global Surgery surgical indicators has not been done. We aimed to undertake a complete situation analysis of SAO system preparedness, service delivery, and financial risk protection using the core surgical indicators proposed by the Commission in Colombia, an upper-middle-income country. METHODS: Data to inform the six core surgical system indicators were abstracted from the Colombian national health information system and the most recent national health survey done in 2007. Geographical access to a Bellwether hospital (defined as a hospital capable of providing essential and emergency surgery) within 2 h was assessed by determining 2 h drive time boundaries around Bellwether facilities and the population within and outside these boundaries. Physical 2 h access to a Bellwether was determined by the presence of a motor vehicle suitable for individual transportation. The Department Administrativo Nacional de Estadística population projection for 2016 and 2018 was used to calculate the SAO provider density. Total operative volume was calculated for 2016 and expressed nationally per 100â000 population. The total number of postoperative deaths that occurred within 30 days of a procedure was divided by the total operative volume to calculate the all-cause, non-risk-adjusted postoperative mortality. The proportion of the population subject to impoverishing costs was calculated by subtracting the baseline number of impoverished individuals from those who fell below the poverty line once out-of-pocket payments were accounted for. Individuals who incurred out-of-pocket payments that were more than 10% of their annual household income were considered to have experienced catastrophic expenditure. Using GIS mapping, SAO system preparedness, service delivery, and cost protection were also contextualised by socioeconomic status. FINDINGS: In 2016, at least 7·1 million people (15·1% of the population) in Colombia did not have geographical access to SAO services within a 2 h driving distance. SAO provider density falls short of the Commission's minimum target of 20 providers per 100â000 population, at an estimated density of 13·7 essential SAO health-care providers per 100â000 population in 2018. Lower socioeconomic status of a municipality, as indicated by proportion of people enrolled in the subsidised insurance regime, was associated with a smaller proportion of the population in the municipality being within 2 h of a Bellwether facility, and the most socioeconomically disadvantaged municipalities often had no SAO providers. Furthermore, Colombian providers appear to be working at or beyond capacity, doing 2690-3090 procedures per 100â000 population annually, but they have maintained a relatively low median postoperative mortality of 0·74% (IQR 0·48-0·84). Finally, out-of-pocket expenses for indirect health-care costs were a key barrier to accessing surgical care, prompting 3·1 million (6·4% of the population) individuals to become impoverished and 9·5 million (19·4% of the population) individuals to incur catastrophic expenditures in 2007. INTERPRETATION: We did a non-modelled, indicator-based situation analysis of the Colombian SAO system, finding that it has not yet met, but is working towards achieving, the targets set by the Lancet Commission on Global Surgery. The observed interdependence of these indicators and correlation with socioeconomic status are consistent with well recognised factors and outcomes of social, health, and health-care inequity. The internal consistency observed in Colombia's situation analysis validates the use of the indicators and has now informed development of an early national SAO plan in Colombia, to set a data-informed stage for implementation and evaluation of timely, safe, and affordable SAO health care, within the National Public Health Decennial Plan, which is due in 2022. FUNDING: Zoll Medical.
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Indicadores de Calidad de la Atención de Salud , Procedimientos Quirúrgicos Operativos/normas , Colombia , Humanos , Sociedades MédicasRESUMEN
Despite its peculiar distribution, the biology of the southernmost bat species in the world, the Chilean myotis (Myotis chiloensis), has garnered little attention so far. The species has a north-south distribution of c. 2800 km, mostly on the eastern side of the Andes mountain range. Use of extended torpor occurs in the southernmost portion of the range, putting the species at risk of bat white-nose syndrome, a fungal disease responsible for massive population declines in North American bats. Here, we examined how geographic distance and topology would be reflected in the population structure of M. chiloensis along the majority of its range using a double digestion RAD-seq method. We sampled 66 individuals across the species range and discovered pronounced isolation-by-distance. Furthermore, and surprisingly, we found higher degrees of heterozygosity in the southernmost populations compared to the north. A coalescence analysis revealed that our populations may still not have reached secondary contact after the Last Glacial Maximum. As for the potential spread of pathogens, such as the fungus causing WNS, connectivity among populations was noticeably low, especially between the southern hibernatory populations in the Magallanes and Tierra del Fuego, and more northerly populations. This suggests the probability of geographic spread of the disease from the north through bat-to-bat contact to susceptible populations is low. The study presents a rare case of defined population structure in a bat species and warrants further research on the underlying factors contributing to this. See the graphical abstract here. https://doi.org/10.25387/g3.12173385.
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Ascomicetos , Quirópteros , Micosis , Animales , Ascomicetos/genética , Quirópteros/genética , Genómica , Micosis/genética , Micosis/veterinaria , NarizRESUMEN
BACKGROUND: Lymph node (LN) involvement is a poor prognostic factor for malignant pleural mesothelioma (MPM). However, to our knowledge, postresection outcomes of node-negative (cN0/pN0), occult pathologic nodal disease (cN0/pN+), and clinical node-positive disease (cN+) have not been compared to date. PATIENTS AND METHODS: The National Cancer Data Base was queried for newly diagnosed, resected MPM with known clinical/pathologic LN information. Three cohorts were compared: cN0/pN0, cN+, and cN0/pN+. Multivariable logistic regression examined predictors of pathologic nodal upstaging. Kaplan-Meier analysis with propensity matching assessed overall survival (OS); multivariate Cox proportional hazards modeling examined predictors thereof. RESULTS: Of 1369 patients, 687 (50%) had cN0/pN0, 457 (33%) cN+, and 225 (16%) cN0/pN+ disease. Median follow-up was 29 months. In patients with cN0 disease, factors associated with pathologic nodal upstaging were younger age, greater number of examined LNs, and nonsarcomatoid histology (P < .05 for all). Relative to pN0 cases, occult LN involvement (65% being pN2) was associated with 51% higher hazard of mortality on multivariate analysis (P = .005). Following propensity matching, the OS of cN0/pN+ was similar to cN+ cases (P = .281). On multivariate analysis, the number of involved LNs (continuous variable, P = .013), but not nodal tumor, node, metastasis (TNM) classification or LN ratio (P > .05 for both), was associated with OS. CONCLUSION: Detecting occult nodal disease during resection for cN0 MPM is associated with poorer prognosis, with similar survival as cN+ cases, underscoring the importance of routine preoperative pathologic nodal assessment for potentially resectable MPM. The number of involved LNs (rather than current location-based classification) may provide more robust prognostic stratification for future TNM staging.
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Escisión del Ganglio Linfático/mortalidad , Mesotelioma Maligno/patología , Neoplasias Pleurales/patología , Anciano , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Mesotelioma Maligno/cirugía , Persona de Mediana Edad , Neoplasias Pleurales/cirugía , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Uniform light fluence distribution for patients undergoing photodynamic therapy (PDT) is critical to ensure predictable PDT outcomes. However, current practice when delivering intrapleural PDT uses a point source to deliver light that is monitored by seven isotropic detectors placed within the pleural cavity to assess its uniformity. We have developed a real-time infrared (IR) tracking camera to follow the movement of the light point source and the surface contour of the treatment area. The calculated light fluence rates were matched with isotropic detectors using a two-correction factor method and an empirical model that includes both direct and scattered light components. Our clinical trial demonstrated that we can successfully implement the IR navigation system in 75% (15/20) of the patients. Data were successfully analyzed in 80% (12/15) patients because detector locations were not available for three patients. We conclude that it is feasible to use an IR camera-based system to track the motion of the light source during PDT and demonstrate its use to quantify the uniformity of light distribution, which deviated by a standard deviation of 18% from the prescribed light dose. The navigation system will fail when insufficient percentage of light source positions is obtained (<30%) during PDT.
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Clorofila/análogos & derivados , Rayos Infrarrojos , Fotoquimioterapia/métodos , Neoplasias Pleurales/tratamiento farmacológico , Clorofila/química , HumanosRESUMEN
Distal axonopathy is a recognized pathological feature of amyotrophic lateral sclerosis (ALS). In the peripheral nerves of ALS patients, motor axon loss elicits a Wallerian-like degeneration characterized by denervated Schwann cells (SCs) together with immune cell infiltration. However, the pathogenic significance of denervated SCs accumulating following impaired axonal growth in ALS remains unclear. Here, we analyze SC phenotypes in sciatic nerves of ALS patients and paralytic SOD1G93A rats, and identify remarkably similar and specific reactive SC phenotypes based on the pattern of S100ß, GFAP, isolectin and/or p75NTR immunoreactivity. Different subsets of reactive SCs expressed colony-stimulating factor-1 (CSF1) and Interleukin-34 (IL-34) and closely interacted with numerous endoneurial CSF-1R-expressing monocyte/macrophages, suggesting a paracrine mechanism of myeloid cell expansion and activation. SCs bearing phagocytic phenotypes as well as endoneurial macrophages expressed stem cell factor (SCF), a trophic factor that attracts and activates mast cells through the c-Kit receptor. Notably, a subpopulation of Ki67+ SCs expressed c-Kit in the sciatic nerves of SOD1G93A rats, suggesting a signaling pathway that fuels SC proliferation in ALS. c-Kit+ mast cells were also abundant in the sciatic nerve from ALS donors but not in controls. Pharmacological inhibition of CSF-1R and c-Kit with masitinib in SOD1G93A rats potently reduced SC reactivity and immune cell infiltration in the sciatic nerve and ventral roots, suggesting a mechanism by which the drug ameliorates peripheral nerve pathology. These findings provide strong evidence for a previously unknown inflammatory mechanism triggered by SCs in ALS peripheral nerves that has broad application in developing novel therapies.
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Esclerosis Amiotrófica Lateral/patología , Inflamación/metabolismo , Interleucinas/metabolismo , Factor Estimulante de Colonias de Macrófagos/metabolismo , Células de Schwann/metabolismo , Factor de Células Madre/metabolismo , Esclerosis Amiotrófica Lateral/metabolismo , Animales , Axones/patología , Modelos Animales de Enfermedad , Humanos , Masculino , Neuronas Motoras/patología , Neuroglía/metabolismo , Ratas TransgénicasRESUMEN
Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons accompanied by proliferation of reactive microglia in affected regions. However, it is unknown whether the hematopoietic marker CD34 can identify a subpopulation of proliferating microglial cells in the ALS degenerating spinal cord. Immunohistochemistry for CD34 and microglia markers was performed in lumbar spinal cords of ALS rats bearing the SOD1G93A mutation and autopsied ALS and control human subjects. Characterization of CD34-positive cells was also performed in primary cell cultures of the rat spinal cords. CD34 was expressed in a large number of cells that closely interacted with degenerating lumbar spinal cord motor neurons in symptomatic SOD1G93A rats, but not in controls. Most CD34+ cells co-expressed the myeloid marker CD11b, while only a subpopulation was stained for Iba1 or CD68. Notably, CD34+ cells actively proliferated and formed clusters adjacent to damaged motor neurons bearing misfolded SOD1. CD34+ cells were identified in the proximity of motor neurons in autopsied spinal cord from sporadic ALS subjects but not in controls. Cell culture of symptomatic SOD1G93A rat spinal cords yielded a large number of CD34+ cells exclusively in the non-adherent phase, which generated microglia after successive passaging. A yet unrecognized CD34+ cells, expressing or not the microglial marker Iba1, proliferate and accumulate adjacent to degenerating spinal motor neurons, representing an intriguing cell target for approaching ALS pathogenesis and therapeutics.
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Esclerosis Amiotrófica Lateral/patología , Antígenos CD34/análisis , Microglía/patología , Neuronas Motoras/patología , Esclerosis Amiotrófica Lateral/genética , Animales , Proliferación Celular , Células Cultivadas , Humanos , Masculino , Microglía/citología , Mutación Puntual , Pliegue de Proteína , Ratas , Médula Espinal/patología , Superóxido Dismutasa-1/análisis , Superóxido Dismutasa-1/genéticaRESUMEN
Age is a recognized risk factor for amyotrophic lateral sclerosis (ALS), a paralytic disease characterized by progressive loss of motor neurons and neuroinflammation. A hallmark of aging is the accumulation of senescent cells. Yet, the pathogenic role of cellular senescence in ALS remains poorly understood. In rats bearing the ALS-linked SOD1G93A mutation, microgliosis contribute to motor neuron death, and its pharmacologic downregulation results in increased survival. Here, we have explored whether gliosis and motor neuron loss were associated with cellular senescence in the spinal cord during paralysis progression. In the lumbar spinal cord of symptomatic SOD1G93A rats, numerous cells displayed nuclear p16INK4a as well as loss of nuclear Lamin B1 expression, two recognized senescence-associated markers. The number of p16INK4a-positive nuclei increased by four-fold while Lamin B1-negative nuclei increased by 1,2-fold, respect to non-transgenic or asymptomatic transgenic rats. p16INK4a-positive nuclei and Lamin B1-negative nuclei were typically localized in a subset of hypertrophic Iba1-positive microglia, occasionally exhibiting nuclear giant multinucleated cell aggregates and abnormal nuclear morphology. Next, we analyzed senescence markers in cell cultures of microglia obtained from the spinal cord of symptomatic SOD1G93A rats. Although microglia actively proliferated in cultures, a subset of them developed senescence markers after few days in vitro and subsequent passages. Senescent SOD1G93A microglia in culture conditions were characterized by large and flat morphology, senescence-associated beta-Galactosidase (SA-ß-Gal) activity as well as positive labeling for p16INK4a, p53, matrix metalloproteinase-1 (MMP-1) and nitrotyrosine, suggesting a senescent-associated secretory phenotype (SASP). Remarkably, in the degenerating lumbar spinal cord other cell types, including ChAT-positive motor neurons and GFAP-expressing astrocytes, also displayed nuclear p16INK4a staining. These results suggest that cellular senescence is closely associated with inflammation and motor neuron loss occurring after paralysis onset in SOD1G93A rats. The emergence of senescent cells could mediate key pathogenic mechanisms in ALS.
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The Cimicidae is a family of blood-dependent ectoparasites in which dispersion capacity is greatly associated with host movements. Bats are the ancestral and most prevalent hosts for cimicids. Cimicids have a worldwide distribution matching that of their hosts, but the global classification is incomplete, especially for species outside the most common Cimicidae taxa. In this study, we place a little-studied cimicid species, Bucimex chilensis, within a comprehensive molecular phylogeny of Cimicidae by sequencing the genomic regions of this and other closely related species. For this study, we collected B. chilensis females from Myotis chiloensis in Tierra del Fuego, 1,300 km further south than previously known southernmost distribution boundary. We also sequenced COI regions from Primicimex cavernis, a species which together with B. chilensis comprise the entire subfamily Primiciminae. Using Bayesian posterior probability and maximum-likelihood approaches, we found that B. chilensis and P. cavernis clustered close to each other in the molecular analyses, receiving support from similar morphological features, agreeing with the morphology-based taxonomic placement of the two species within the subfamily Primiciminae. We also describe a previously unrecognized morphological adaptation of the tarsal structure, which allows the austral bat ectoparasite, B. chilensis, to cling on to the pelage of its known host, the Chilean myotis (Myotis chiloensis). Through a morphological study and behavioral observation, we elucidate how this tarsal structure operates, and we hypothesize that by clinging in the host pelage, B. chilensis is able to disperse effectively to new areas despite low host density. This is a unique feature shared by P. cavernis, the only other species in Primiciminae.
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The most popular approach to treating symptomatic cervical disk disease is anterior cervical discectomy and fusion. Although this procedure has significant long-term clinical success, it is associated with progressive adjacent segment degeneration with an annual incidence of â¼3%. Total disk arthroplasty was designed as an alternative to fusion that could preserve segmental motion at the operative level and potentially delay or prevent adjacent-level breakdown. The etiology of adjacent segment pathology (ASP) is multifactorial, and it is likely that most cases of ASP are unavoidable. When attempting to surgically prevent ASP, it is important to consider nonfusion alternatives, be judicious in one's level selection, and attempt to restore sagittal alignment. When ASP becomes a clinical problem, it is important to have an algorithm for how best to treat it.
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Vértebras Cervicales , Degeneración del Disco Intervertebral/cirugía , Desplazamiento del Disco Intervertebral/cirugía , Radiculopatía/prevención & control , Discectomía/efectos adversos , Humanos , Complicaciones Posoperatorias/prevención & control , Fusión Vertebral/efectos adversosRESUMEN
BACKGROUND: Stereotactic body radiation therapy (SBRT) is standard for medically inoperable stage I non-small-cell lung cancer (NSCLC) and is emerging as a surgical alternative in operable patients. However, limited long-term outcomes data exist, particularly according to operability. We hypothesized long-term local control (LC) and cancer-specific survival (CSS) would not differ by fractionation schedule, tumor size or location, or operability status, but overall survival (OS) would be higher for operable patients. PATIENTS AND METHODS: All consecutive patients with stage I (cT1-2aN0M0) NSCLC treated with SBRT from June 2009 to July 2013 were assessed. Thoracic surgeon evaluation determined operability. Local failure was defined as growth following initial tumor shrinkage or progression on consecutive scans. LC, CSS, and OS were calculated using Cox proportional hazards regression. RESULTS: A total of 186 patients (204 lesions) were analyzed. Most patients were inoperable (82%) with Eastern Cooperative Oncology Group performance status of 1 (59%) or 2 (26%). All lesions received biological effective doses ≥ 100 Gy most commonly (94%) in 3 to 5 fractions. The median follow-up was 4.0 years. LC at 2 and 5 years were 95.6% (95% confidence interval, 92%-99%) and 93.7% (95% confidence interval, 90%-98%), respectively. Compared with operable patients, inoperable patients did not have significant differences in 5-year LC (93.1% vs. 96.7%; P = .49), nodal failure (31.4% vs. 11.0%; P = .12), distant failure (12.2% vs. 10.4%; P = .98), or CSS (80.6% vs. 91.0%; P = .45) but trended towards worse OS (34.2% vs. 45.3%; P = .068). Tumor size, location, and fractionation did not significantly influence outcomes. CONCLUSIONS: SBRT has excellent, durable LC and CSS rates for early-stage NSCLC, although inoperable patients had somewhat lower OS than operable patients, likely owing to greater comorbidities.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Neoplasias Pulmonares/radioterapia , Radiocirugia , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Fraccionamiento de la Dosis de Radiación , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Análisis de Supervivencia , Resultado del Tratamiento , Carga TumoralRESUMEN
INTRODUCTION: Postoperative C5 nerve root palsy is a known complication after cervical surgery. The effect of increasing number of levels fused on the prevalence of C5 palsy after anterior cervical diskectomy and fusion (ACDF) is unclear. METHODS: Medical records of ACDF patients that included the C4-5 level at one institution were retrospectively reviewed. C5 palsy was defined as motor decline of the deltoid and/or biceps brachii muscle function by at least 1 level on standard manual muscle testing. RESULTS: A total of 196 patients met the inclusion criteria, with no significant differences noted between groups undergoing single- or multi-level ACDF. The overall C5 palsy rate was 5.1%. Palsy rates were not statistically significant based on the number of levels fused. Six of the 10 patients with C5 palsy had complete recovery of motor strength, whereas 2 patients had at least some level of strength recovery. CONCLUSION: The overall C5 palsy rate was 5.1% for all patients undergoing up to four-level ACDF. The rate of postoperative motor decline was lowest in the patients undergoing two-level ACDF and highest in the single-level group, but this finding did not reach statistical significance. The prognosis for strength recovery by final follow-up is excellent. LEVEL OF EVIDENCE: Level III, Case-control.