Late infantile neuronal ceroid lipofuscinosis is an autosomal recessive disease caused by mutations in the CLN2/TPP1 gene, with secondary enzyme deficiency. In classical phenotypes, initial symptoms ...include seizures and delayed language development between 2 and 4 years of age. This article describes the presentation of CLN2 disease in a cohort of Colombian patients, as well as the impact of treatment on the course and progression of the disease.
Case series report of 8 patients with a confirmed diagnosis of neuronal ceroid lipofuscinosis treated with cerliponase alfa who remained on clinical and paraclinical follow-up for up to 24 months before and after treatment.
An atypical phenotype, associated with initial symptoms and late diagnosis, was present in 5/8 patients. The most frequent symptoms were seizures and developmental delay, with age of onset at 24 months (classical phenotype) and 48 months (atypical phenotype). A novel mutation (c.1438G > A) was found in two siblings. All of the patients received cerliponase alfa, and there were no serious adverse events. No decline in the clinical status greater than 2 points on Hamburg, Weill Cornell and CNL2 clinical assessment scale was observed during follow-up after treatment initiation.
This is the first case series reported for neuronal ceroid lipofuscinosis patients in Colombia. In contrast with other reports, the majority of cases reported here displayed an atypical phenotype. Our study highlights the importance of early diagnosis and timely initiation of therapy, which is a feasible therapy, well tolerated by patients and accepted by caregivers in this country, generating a positive impact in the quality of life of CLN2 patients and on disease outcome.
Balanced general anesthesia, the most common management strategy used in anesthesia care, entails the administration of different drugs together to create the anesthetic state. Anesthesiologists ...developed this approach to avoid sole reliance on ether for general anesthesia maintenance. Balanced general anesthesia uses less of each drug than if the drug were administered alone, thereby increasing the likelihood of its desired effects and reducing the likelihood of its side effects. To manage nociception intraoperatively and pain postoperatively, the current practice of balanced general anesthesia relies almost exclusively on opioids. While opioids are the most effective antinociceptive agents, they have undesirable side effects. Moreover, overreliance on opioids has contributed to the opioid epidemic in the United States. Spurred by concern of opioid overuse, balanced general anesthesia strategies are now using more agents to create the anesthetic state. Under these approaches, called "multimodal general anesthesia," the additional drugs may include agents with specific central nervous system targets such as dexmedetomidine and ones with less specific targets, such as magnesium. It is postulated that use of more agents at smaller doses further maximizes desired effects while minimizing side effects. Although this approach appears to maximize the benefit-to-side effect ratio, no rational strategy has been provided for choosing the drug combinations. Nociception induced by surgery is the primary reason for placing a patient in a state of general anesthesia. Hence, any rational strategy should focus on nociception control intraoperatively and pain control postoperatively. In this Special Article, we review the anatomy and physiology of the nociceptive and arousal circuits, and the mechanisms through which commonly used anesthetics and anesthetic adjuncts act in these systems. We propose a rational strategy for multimodal general anesthesia predicated on choosing a combination of agents that act at different targets in the nociceptive system to control nociception intraoperatively and pain postoperatively. Because these agents also decrease arousal, the doses of hypnotics and/or inhaled ethers needed to control unconsciousness are reduced. Effective use of this strategy requires simultaneous monitoring of antinociception and level of unconsciousness. We illustrate the application of this strategy by summarizing anesthetic management for 4 representative surgeries.
Agave durangensis is an endemic species that occurs in a reduced area in southern Durango and northern Zacatecas, Mexico. We analyzed the genetic variability of three populations of the species using ...two pairs of Inverse-Sequence-Tagged-Repeat primers and nine morphological characters to determine the species of the morphologically variable populations. The primers generated characteristic amplification profiles, which distinguished between populations of A. durangensis and revealed interspecific variability when compared with individuals of A. asperrima. Some incongruence between morphological and molecular variability was detected. High genetic variability was indicated by an elevated level of polymorphism (24.18–61.50%) among 91 genetic loci amplified and by the level of gene diversity (0.0807–0.2337) among populations. Genetic differentiation (0.0328–0.4857), gene flow (0.5294–14.7511), genetic distance (0.0200–0.3019), and genetic identity (0.7653–0.9802) among populations suggested that one of the three populations of A. durangensis is in a present advanced diversification process but may still maintain some level of gene flow with the other two populations. Urgent conservation efforts, including protection from harvest, should be addressed for maintaining the genetic variability of the natural populations of A. durangensis. Agave durangensis es una especie endémica que crece en un área reducida del sur de Durango y norte de Zacatecas, México. Analizamos la variabilidad genética de tres poblaciones de esa especie usando dos pares de iniciadores de los marcadores de Repetición de Secuencias Inversas Marcadas (ISTR por sus siglas en inglés) y nueve atributos morfológicos para determinar las especies de las poblaciones morfológicamente muy variables. Los iniciadores generaron perfiles de amplificación característicos, mostrando su capacidad para distinguir entre poblaciones de A. durangensis y para revelar variabilidad intereespecífica cuando los perfiles se compararon con los de A. asperrima. Incongruencia entre la variabilidad morfológica y la molecular fue detectada. Alta variabilidad genética fue encontrada, indicada por los elevados niveles de polimorfismo (24.18–61.50 %) entre 91 loci genéticos amplificados y por los valores de diversidad génica (0.0807–0.2337) entre poblaciones. Diferenciación genética interpoblacional (0.0328–0.4857), flujo genético (0.5294–14.7511), distancia genética (0.0200–0.3019) y la identidad genética (0.7653–0.9802) sugieren que una de las tres poblaciones de A. durangensis se encuentra en un proceso actual avanzado de diversificación, pero que aún existe flujo genético con las otras dos poblaciones. Esfuerzos urgentes de conservación incluyendo la protección de recolección se deberían de contemplar para mantener la variabilidad genética de las poblaciones naturales de A. durangensis.
The purely electroweak (EW) cross section for the production of two jets in association with a Z boson, in proton-proton collisions at sqrt(s) = 8 TeV, is measured using data recorded by the CMS ...experiment at the CERN LHC, corresponding to an integrated luminosity of 19.7 inverse femtobarns. The electroweak cross section for the lljj final state (with l = e or mu and j representing the quarks produced in the hard interaction) in the kinematic region defined by Mll > 50 GeV, Mjj > 120 GeV, transverse momentum ptj > 25 GeV, and pseudorapidity abs(etaj) < 5, is found to be sigmaEW(lljj) = 174 +/- 15 (stat) +/- 40 (syst) fb, in agreement with the standard model prediction. The associated jet activity of the selected events is studied, in particular in a signal-enriched region of phase space, and the measurements are found to be in agreement with QCD predictions.
There is an increasing need for accurate groundwater-level (GWL) prediction to support effective seasonal water management. It is desirable for forecasting tools to be not only accurate but also ...accessible for decision-makers. We test the Prophet forecasting procedure, an open-source code released by Facebook, to address these challenges. It is based on an additive model considering non-periodic changes and periodic components in a Bayesian framework with easily-interpretable parameters. Predictions of daily GWL data in an area affected by pumping near a tourist complex in the Ramsar wetland area of Doñana (Spain) are compared to other forecasting methods. Prophet outperforms most methods in predicting GWL making it a fast and flexible forecasting tool for hydrologists and water managers. Furthermore, it allows gaining insight into the influence of each component of the forecast separately, helping to assess the hydrodynamic response to external drivers such as groundwater pumping.
Perioperative Management of Pheochromocytoma Naranjo, Julian, DO; Dodd, Sarah, MD; Martin, Yvette N., MD, PhD
Journal of cardiothoracic and vascular anesthesia,
08/2017, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Pheochromocytomas are rare neuroendocrine tumors that produce and store catecholamines. Without adequate preparation, the release of excessive amounts of catecholamines, especially during anesthetic ...induction or during surgical removal, can produce life-threatening cardiovascular complications. This review focuses on the perioperative management of pheochromocytoma/paragangliomas, initially summarizing the clinical aspects of the disease and then highlighting the current evidence available for preoperative, intraoperative, and postoperative anesthetic management.
This work is focused on the Almonte‐Marismas aquifer located within Doñana Natural Space (SW Spain); this aquifer is threatened by droughts, irrigation‐driven groundwater overexploitation, urban use, ...and the potential reactivation of gas extraction and storage projects. We present ground deformation measurements from Sentinel‐1 Interferometric Synthetic Aperture Radar (InSAR) data ranging from 1 to 2.5 cm, covering ∼2,500 km2 from 2014 to 2020. Detecting spatially distributed ground deformation over this agricultural area is challenging due to the low‐coherence radar signals; consequently, the ground movement results are on the same order of magnitude as the errors associated with InSAR data. We have approached this issue by considering auxiliary information such as groundwater levels, climatic time series, and pumping rates and analyzing their spatio‐temporal connections to ground displacements. We correlate InSAR and hydrogeological information through wavelet analysis, developing a Python package that allows applying the same methodology in other similar study areas. For the first time in the Doñana area, a significant relationship between distances to pumping wells and the displacement extent is detected. Moreover, other subsidence‐related triggering factors are identified, such as the soil moisture balance, clay shrinking‐swelling processes, and creep of geological formations. These results are highly valuable to support aquifer management decisions in the Doñana Natural Space; in this border region, three groundwater bodies were officially declared overexploited in 2020. Our findings provide a ground motion baseline assessment to help differentiate historical variations from any future anthropogenic effect in this complex marsh land ecosystem.
Plain Language Summary
This work is focused on Doñana Natural Space (SW Spain), which integrates the Doñana National Park and the Doñana Natural Park in a single space. Doñana has acquired the highest protected area categories that a natural area can receive from international conservation organizations. However, Doñana's ability to support biodiversity is under constant threat due to droughts, groundwater overexploitation for irrigation, urban use, and the reactivation of a gas extraction and storage project. This study presents ground deformation measurements in the Doñana area derived from Earth observation data ranging from 1 to 2.5 cm from 2014 to 2020. The work relates ground displacement, groundwater and climatic information through mathematical tools. For the first time in the Doñana area, a significant relationship between distances to pumping wells and the displacement extent is detected. These results are highly valuable to support aquifer management decisions in the Doñana Natural Space. Our findings provide a ground motion baseline assessment that will help differentiate historical variations from any future anthropogenic effect in this complex marsh land ecosystem.
Key Points
Integrated Interferometric Synthetic Aperture Radar and hydrogeological analysis has shown displacements up to 2.5 cm/year on the aquifer that hosts the Doñana Natural Space
Wavelet method with a new Python package allows for integrated displacement, groundwater level, climatic and pumping time series analyses
The results provide a ground motion baseline to differentiate natural variations from future anthropogenic effects in the Doñana area
Summary
Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that ...monocyte subsets (classical, intermediate and non‐classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non‐classical monocytes in patients compared with controls. With this finding, we focused on studying the phenotype of non‐classical monocytes in the present study. An increase in activation and differentiation markers, such as CD64, CD86, the percentage of tumor necrosis factor‐α+ cells and exposure of phosphatidylserine, were recorded in the non‐classical monocytes of patients compared with controls. Moreover, a significant decrease in the expression of CX3CR1 with a corresponding increase in the expressions of CCR2, CCR5, CD11b and CD54 was detected in the non‐classical monocytes of patients in comparison with that of the controls. Significant increases in the frequency of microparticles from endothelium and in the concentrations of interleukin‐6 (IL‐6), IL‐8 and IL‐10 were noted in the plasma of patients. These findings demonstrate that in patients with dengue, non‐classical monocytes are activated, exhibiting a phenotype associated with more differentiation, produces tumor necrosis factor‐α and has a profile of less endothelial surveillance closer to the cellular migration. These changes were associated with hepatic compromise, endothelial alteration and high concentration of circulating cytokines. Hence, alterations of non‐classical monocytes seem to be associated with the immunopathology of dengue infection.
Changes in the non‐classical monocytes of dengue patients are associated with different manifestations of this disease such as hepatic compromise, pro‐inflammatory response, or endothelial damage. Therefore, non‐classical monocytes may contribute to the immunopathology of dengue.
Highlights • Vestibular evoked myogenic potentials recorded simultaneously from neck and limb muscles during a quiet standing task. • Robust evidence provided for the increased gain of the ...vestibulospinal reflexes under states of fear, anxiety and arousal. • Findings show an association between negative emotional changes and changes in the gain of the vestibulospinal reflexes.
The secretion of cell wall‐degrading enzymes is one of the mechanisms used by necrotrophic fungi to colonize host tissues. However, information about virulence factors of Monilinia spp., the causal ...agents of brown rot in stone fruit, is scarce. Plant cell walls have three main components that are broken down by fungal enzymes: cellulose, hemicellulose and pectin. In order to identify Monilinia laxa candidate proteins involved in pectin hydrolysis, two in vitro approaches were conducted: (i) phenotypic and ecophysiological characterization of growth of the pathogen at different pHs, in glucose‐ and pectin‐containing solid media for 7 days' incubation; and (ii) expression analysis of genes encoding M. laxa pectin methyl esterases (MlPMEs) and rhamnogalacturonan hydrolases (MlRG‐HYDs) after incubation for 0.5, 2, 6, 24 and 48 h in glucose‐ and pectin‐containing liquid media. Phenotypic tests showed the role of carbon source on M. laxa growth rate and aggressiveness, and indicated that pectinases were greatly affected by pH. Gene expression analyses uncovered differences among members of each family of pectinases and between the two families, defining sets of genes expressed at earlier (0.5–6 h) and later (48 h) phases. Notably, the up‐ or down‐regulation of these target genes was carbon source‐dependent. Finally, an in vivo study confirmed the synergistic and complementary role that these genes play in the M. laxa–stone fruit pathosystem. Based on these results, it is hypothesized that MlPME2, MlRG‐HYD1 and MlRG‐HYD2 may be potential virulence factors of M. laxa in the process from infection to colonization.
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