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1.
Rev. neurol. (Ed. impr.) ; 78(4)16-28 feb., 2024. tab, graf
Article in Spanish | IBECS | ID: ibc-230631

ABSTRACT

Objetivo Determinar las características clínicas, electroencefalográficas, terapéuticas y evolutivas de una serie de pacientes oncopediátricos con convulsiones sintomáticas agudas. Pacientes y métodos Efectuamos un análisis descriptivo retrospectivo y prospectivo de registros clínicos de niños oncopediátricos evaluados por neurología en el Centro Ambulatorio Integral de Pacientes Hematooncológicos durante 2017-2021. Incluimos a niños de 1 mes a 17 años con tumores intracraneales y extracraneales que presentaron convulsiones sintomáticas agudas (CSA). Definimos convulsión sintomática aguda según la clasificación de la Liga Internacional contra la Epilepsia de 2010. Clasificamos las crisis epilépticas según la clasificación de la Liga Internacional contra la Epilepsia de 2017. Excluimos a todo paciente con diagnóstico de epilepsia previa y de episodios paroxísticos no epilépticos. Resultados Analizamos 44 casos, con una mediana de 4 años (rango: 1 mes-17 años) y una media de 5,75 meses (rango: 1 mes-11 meses) y 8,33 años (2-17 años). Registramos como principales etiologías la neurotoxicidad y el contexto posquirúrgico, con cuatro pacientes asociados a disnatremias y dos a hipertensión endocraneana. Se realizaron 41 electroencefalogramas, con resultados intercríticos con anormalidades en el ritmo de base, pero sin focos ni paroxismos. No hubo registros críticos. Las convulsiones focales fueron 25 (56,8%), y las generalizadas, 19 (43,18%). El levetiracetam fue el fármaco más utilizado para el tratamiento agudo. Conclusiones Nuestra cohorte muestra que las CSA, en esta población, no evidencian diferencias considerables entre convulsiones focales motoras y generalizadas, y ocurren mayormente en un contexto neurotóxico y posquirúrgico. También se registraron disnatremias e hipertensión endocraneana asociadas a CSA. Los electroencefalogramas poscrisis fueron sin focos o paroxismos y con evolución de las crisis. (AU)


AIM To determine clinical, electroencephalographic, therapeutic and evolutive characteristics of a series of oncopediatric patients with acute symptomatic seizures. PATIENTS AND METHODS We performed a retrospective and prospective descriptive analysis of clinical records of oncopediatric children evaluated by neurology at the comprehensive outpatient Center for Hemato-Oncological Patients during 2017-2021. We included children aged one month to 17 years with intracranial and extracranial tumors who presented with acute symptomatic seizure (ASC). We defined acute symptomatic seizure according to the 2010 International League Against Epilepsy. We classified seizures according to 2017 International League Against Epilepsy classification. We excluded any patient with a diagnosis of previous epilepsy and non-epileptic paroxysmal episodes. RESULTS We analyzed 44 cases with a median of 4 years (range: 1 month-17 years) and mean of 5.75 months (range: 1 month-11 months) and 8.33 years (2-17 years). The main etiologies were neurotoxicity and post-surgical context. Four patients presented dysnatremias and two associated with endocranial hypertension. Forty-one electroencephalograms were performed with intercritical results with abnormalities in the baseline rhythm, but without foci or paroxysms. There were no critical recordings. Focal seizures were 25 (56.8%) and generalized seizures 19 (43.18%). Levetiracetam was the most commonly used drug for acute management. CONCLUSIONS Our cohort shows that ASC, in this population, do not show considerable differences between focal motor and generalized seizures and occur mostly in neurotoxic and post-surgical contexts. Dysnatremias and endocranial hypertension associated with ASC were also recorded. Postcrisis electroencephalograms were without foci or paroxysms and good seizure evolution. (AU)


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Seizures/etiology , Medical Oncology , Pediatrics , Postoperative Period , Electroencephalography , Neurotoxins , Therapeutics , Retrospective Studies , Epidemiology, Descriptive , Prospective Studies
2.
J Fish Biol ; 102(3): 689-706, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36625147

ABSTRACT

Water temperature and flow velocity directly affect the fish swimming capacity, and thus, both variables influence the fish passage through river barriers. Nonetheless, their effects are usually disregarded in fishway engineering and management. This study aims to evaluate the volitional swimming capacity of the northern straight-mouth nase (Pseudochondrostoma duriense), considering the possible effects of water temperature, flow velocity and body size. For this, the maximum distance, swim speed and fatigue time (FT) were studied in an outdoor open-channel flume in the Duero River (Burgos, Spain) against three nominal velocities (1.5, 2.5 and 3 m s-1 ) and temperatures (5.5, 13.5 and 18.5°C), also including the changes between swimming modes (prolonged and sprint). Results showed that a nase of 20.8 cm mean fork length can develop a median swim speed that exceeds 20.7 BL s-1 (4.31 m s-1 ) during a median time of 3.4 s in sprint mode, or 12.2 BL s-1 (2.55 m s-1 ) for 23.7 s in prolonged mode under the warmest scenario. During prolonged swimming mode, fish were able to reach further distances in warmer water conditions for all situations, due to a greater swimming speed and FT, whereas during sprint mode, warmer conditions increased the swim speed maintaining the FT. In conclusion, the studied temperature range and flow velocity range influence fish swimming performance, endurance and distance travelled, although with some differences depending on the swimming mode. The provided information goes a step forward in the definition of real fish swimming capacities, and in turn, will contribute to establish clear passage criteria for thermo-velocity barriers, allowing the calculation of the proportion of fish able to pass a barrier under different working scenarios, as well designing of the optimized solutions to improve the fish passage through river barriers.


Subject(s)
Cypriniformes , Swimming , Animals , Body Size , Temperature
3.
Article in English | MEDLINE | ID: mdl-36232190

ABSTRACT

(1) Background: The preoccupation related to the fall, also called fear of falling (FOF) by some authors is of interest in the fields of geriatrics and gerontology because it is related to the risk of falling and subsequent morbidity of falling. This study seeks to classify the acceleration patterns of the center of mass during walking in subjects with mild and moderate knee osteoarthritis (KOA) for three levels of FOF (mild, moderate, and high). (2) Method: Center-of-mass acceleration patterns were recorded in all three planes of motion for a 30-meter walk test. A convolutional neural network (CNN) was implemented for the classification of acceleration signals based on the different levels of FOF (mild, moderate, and high) for two KOA conditions (mild and moderate). (3) Results: For the three levels of FOF to fall and regardless of the degree of KOA, a precision of 0.71 was obtained. For the classification considering the three levels of FOF and only for the mild KOA condition, a precision of 0.72 was obtained. For the classification considering the three levels of FOF and only the moderate KOA condition, a precision of 0.81 was obtained, the same as in the previous case, and finally for the classification for two levels of FOF, a high vs. moderate precision of 0.78 was obtained. For high vs. low, a precision of 0.77 was obtained, and for the moderate vs. low, a precision of 0.8 was obtained. Finally, when considering both KOA conditions, a 0.74 rating was obtained. (4) Conclusions: The classification model based on deep learning (CNN) allows for the adequate discrimination of the acceleration patterns of the moderate class above the low or high FOF.


Subject(s)
Fear , Osteoarthritis, Knee , Acceleration , Aged , Humans , Walking
4.
Sci Total Environ ; 830: 154613, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35306074

ABSTRACT

River connectivity is essential for the resilience of fish assemblages and populations and is a priority goal to reach good ecological status for river systems. Increasing knowledge on the functionality of restoration tools such as fishways is relevant for future management strategies. The present two-year assessment showed clear ecological contributions of different types of multispecies fishways in the fish assemblage of a strongly modified Mediterranean-type river. Just after their implementation, early and extended use by dominant river-resident fish of both naturelike and technical fishways were observed. All fishways were used in different seasons, especially during the migratory periods by potamodromous cyprinids, suggesting a possible use as migration corridors. Fishways also may provide compensatory habitats for small and juvenile individuals throughout the annual cycles, mostly for rheophilic fish inside nature-like bypasses and for limnophilics inside technical types. Fluvial habitat characteristics and lower flow variability inside the fishways could favour their role as a fish refuge, mainly to juveniles of cyprinids, in heavily regulated rivers where large flow fluctuations occurred. Nature-like fishways could be a better option to function as a compensatory habitat for rheophilic cyprinids in Mediterranean-type Rivers, even more because their use by large nonnative limnophilics seems to be very scarce. However, technical fishways could offer the opportunity to establish control traps of some nonnative fish, which could be of interest to reduce the risk of spreading invasive fish. Therefore, fish ecology and local hydrology should drive the decision between the types to implement. The obtained information on the ecological functionality of multispecies fishways should be considered for applying successful river restorations that are demanded by water and wildlife management schemes (e.g., the European Water Framework Directive).


Subject(s)
Ecosystem , Rivers , Animals , Fishes , Hydrology , Water
5.
Environ Sci Pollut Res Int ; 29(21): 31749-31760, 2022 May.
Article in English | MEDLINE | ID: mdl-35015235

ABSTRACT

Odiel river basin is located in the Iberian Pyritic Belt (IPB) and mostly of its tributaries are severely affected by acid mine drainage (AMD). It is originated when pyritic minerals from abandoned mines, especially mineral residues from waste rock dams, get in contact with air and water. Fifteen sampling points were chosen to analyze interactions between diatom communities and water hydrogeochemistry. Considering physicochemical characteristics, sampling points were assigned as highly, moderately, and unpolluted by AMD. No correlation was observed between ecological diversity indexes and physico-chemical parameters. However, a dependency relationship between diatom species distribution and specific pH, conductivity, redox potential, sulfate, and metal concentrations was observed. Cluster analysis based on Pearson correlation and rs values of the non-parametric Spearman correlation allowed to identify Pinnularia acidophila, Pinnularia subcapitata var. elongata, and Eunotia exigua as the main bioindicators of AMD-polluted Odiel streams. Finally, a principal component analysis led to associate the most abundant diatoms species to specific physico-chemical parameters.


Subject(s)
Diatoms , Water Pollutants, Chemical , Acids/analysis , Environmental Monitoring , Minerals/analysis , Rivers/chemistry , Spain , Water/analysis , Water Pollutants, Chemical/analysis
6.
Sensors (Basel) ; 21(20)2021 Oct 18.
Article in English | MEDLINE | ID: mdl-34696122

ABSTRACT

Stepped fishways are structures that allow the free movement of fish in transversal obstacles in rivers. However, the lack of or incorrect maintenance may deviate them from this objective. To handle this problem, this research work presents a novel low-cost sensor network that combines fishway hydraulics with neural networks programmed in Python (Keras + TensorFlow), generating the first autonomous obstruction/malfunction detection system for stepped fishways. The system is based on a network of custom-made ultrasonic water level nodes that transmit data and alarms remotely and in real-time. Its performance was assessed in a field study case as well as offline, considering the influence of the number of sensing nodes and obstruction dimensions. Results show that the proposed system can detect malfunctions and that allows monitoring of the hydraulic performance of the fishway. Consequently, it optimizes the timing of maintenance on fishways and, thus, has the potential of automatizing and reducing the cost of these operations as well as augmenting the service of these structures. Therefore, this novel tool is a step forward to achieve smart fishway management and to increase their operability.


Subject(s)
Fishes , Rivers , Animals
7.
Article in English | MEDLINE | ID: mdl-34444203

ABSTRACT

The Odiel River (SW Spain) is one of the most cited rivers in the scientific literature due to its high pollution degree, generated by more than 80 sulphide mines' (mostly unrestored) contamination in the Iberian Pyritic Belt (IPB), that have been exploited for more than 5000 years. Along the river and its tributaries, the physico-chemical parameters and diatoms, from 15 sampling points, were analyzed in the laboratory. Physico-chemical parameters, water chemical analysis, together with richness and Shannon-Wiener indexes were integrated in a matrix. An initial graphical treatment allowed the definition and proposal of a functioning system model, as well as the establishment of cause-effect relationships between pollution and its effects on biota. Then, the proposed model was statistically validated by factor analysis. For acidic pH waters, high values of Eh, TDS, sulphate, ∑REE and ∑Ficklin were found, while diatomologic indicators took low values. Thus, factor analysis was a very effective tool for graphical treatment validation as well as for pollution-biota interaction models' formulation, governed by two factors: AMD processes and water balance suffered by the studied river. As a novelty, the cause-effect relationships between high barium concentration and low diversity and richness were demonstrated in the IPB, for the first time.


Subject(s)
Diatoms , Water Pollutants, Chemical , Environmental Monitoring , Models, Statistical , Rivers , Spain , Water , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity
8.
Article in English | MEDLINE | ID: mdl-33924929

ABSTRACT

The Odiel River Basin, located in the Iberian Pyrite Belt (IPB), is heavily affected by acid mine drainage (AMD), which occurs when pyritic minerals from sulfide mining areas are exposed to atmospheric, hydrological or biological weathering. This paper presents a hydrochemical characterization of parameters in the Odiel River Basin by means of Fuzzy Logic and data mining methodologies to determine the seasonal influence of AMD in polluted waters that have not been used before for a basin in this environmental area. This technique was proven to be effective, providing results that could not be achieved by using classic statistics, because it allows us to characterize the different parameters separately and also their relationships in waters affected by AMD in a qualitative manner based on the antecedents and according to the conditions (rules) imposed by the consequents (in this case, the Fe(II) and accumulated rainfall over 30 days). Thus, it was possible to confirm that hydrochemistry is greatly affected by seasonal changes, with a higher pH in the wet season (up to 8.59) compared to 2.12, the minimum pH value reached in the dry season. Accordingly, higher concentrations of most of the metals were observed in the dry season (e.g., up to 4000 mg/L of Fe (II)), with the exception of the values found after the first rains that occur in the early fall. With the use of the Fuzzy Logic technique, it was observed that, during the wet season, lixiviates with a higher Fe content have higher metal concentrations, and in the dry season, the behavior is the opposite.


Subject(s)
Environmental Monitoring , Water Pollutants, Chemical , Fuzzy Logic , Rivers , Seasons , Spain , Water Pollutants, Chemical/analysis
9.
Sci Total Environ ; 767: 144926, 2021 May 01.
Article in English | MEDLINE | ID: mdl-33636778

ABSTRACT

The Altiplano-Puna Plateau holds several shallow lakes, which are very sensitive to climate changes. This work is focused on a high-altitude lake system called Lagunas de Vilama (LVS), located in a complex climatic transition area with scarcity of continuous and homogeneous instrumental records. The objective of this study is to determine the regional spatial-temporal variability of precipitation and evaluate the seasonal and interannual lake responses. We use a lake-surfaces record derived from Landsat images to investigate links with regional precipitations and different climatic forcings. The results reveal that austral summer and autumn precipitations control the variability of the annual lake-surfaces. Also, we found intra-annual and interannual lags in the lake responses to precipitations, and identified several wet and dry stages. Our results show negative trends in precipitations and lake-surfaces, whose were strengthened by a shift to a warm phase of the Atlantic Multidecadal Oscillation in the 1990s. The El Niño Southern Oscillation, Pacific Decadal Oscillation, and Southern Annular Mode also exert a strong influence in the region. This study demonstrates that the variability of LVS lakes is strongly related to the South American Monsoon System dynamics and large-scale climate forcings from the Pacific and Atlantic Oceans. This work provides novel indices which demonstrated to be good indicators of regional hydro-climatological variability for this region of South America.

11.
Article in English | MEDLINE | ID: mdl-35010636

ABSTRACT

Acid Mine Drainage (AMD) results from sulfide oxidation, which incorporates hydrogen ions, sulfate, and metals/metalloids into the aquatic environment, allowing fixation, bioaccumulation and biomagnification of pollutants in the aquatic food chain. Acidic leachates from waste rock dams from pyritic and (to a lesser extent) coal mining are the main foci of Acid Mine Drainage (AMD) production. When AMD is incorporated into rivers, notable changes in water hydro-geochemistry and biota are observed. There is a high interest in the biodiversity of this type of extreme environments for several reasons. Studies indicate that extreme acid environments may reflect early Earth conditions, and are thus, suitable for astrobiological experiments as acidophilic microorganisms survive on the sulfates and iron oxides in AMD-contaminated waters/sediments, an analogous environment to Mars; other reasons are related to the biotechnological potential of extremophiles. In addition, AMD is responsible for decreasing the diversity and abundance of different taxa, as well as for selecting the most well-adapted species to these toxic conditions. Acidophilic and acidotolerant eukaryotic microorganisms are mostly composed by algae (diatoms and unicellular and filamentous algae), protozoa, fungi and fungi-like protists, and unsegmented pseudocoelomata animals such as Rotifera and micro-macroinvertebrates. In this work, a literature review summarizing the most recent studies on eukaryotic organisms and micro-organisms in Acid Mine Drainage-affected environments is elaborated.


Subject(s)
Coal Mining , Water Pollutants, Chemical , Acids , Eukaryota , Rivers , Sulfates/analysis , Water Pollutants, Chemical/analysis
12.
PLoS Negl Trop Dis ; 14(11): e0008786, 2020 11.
Article in English | MEDLINE | ID: mdl-33253144

ABSTRACT

BACKGROUND: Rodent-borne hantaviruses (genus Orthohantavirus) are the etiologic agents causing two human diseases: hemorrhagic fever with renal syndrome (HFRS) in Euroasia; and hantavirus pulmonary syndrome (HPS) in North and South America. In South America fatality rates of HPS can reach up to 35%-50%. The transmission of pathogenic hantaviruses to humans occurs mainly via inhalation of aerosolized excreta from infected rodents. Thus, the epidemiology of HPS is necessarily linked to the ecology of their rodent hosts and the contact with a human, which in turn may be influenced by climatic variability. Here we examined the relationship between climatic variables and hantavirus transmission aim to develop an early warning system of potential hantavirus outbreaks based on ecologically relevant climatic factors. METHODOLOGY AND MAIN FINDINGS: We compiled reported HPS cases in northwestern Argentina during the 1997-2017 period and divided our data into biannual, quarterly, and bimestrial time periods to allow annual and shorter time delays to be observed. To evaluate the relationship of hantavirus transmission with mean temperature and precipitation we used dynamic regression analysis. We found a significant association between HPS incidence and lagged rainfall and temperature with a delay of 2 to 6 months. For the biannual and quarterly models, hantavirus transmission was positively associated with lagged rainfall and temperature; whereas the bimestrial models indicate a direct relationship with the rainfall but inverse for temperature in the second lagged period. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that climate variability plays a significant role in the transmission of hantavirus in northwestern Argentina. The model developed in this study provides a basis for the forecast of potential HPS outbreaks based on climatic parameters. Our findings are valuable for the development of public health policies and prevention strategies to mitigate possible outbreaks. Nonetheless, a surveillance program on rodent population dynamics would lead to a more accurate forecast of HPS outbreaks.


Subject(s)
Climate , Disease Outbreaks/statistics & numerical data , Hantavirus Pulmonary Syndrome/epidemiology , Argentina/epidemiology , Hantavirus Pulmonary Syndrome/transmission , Humans , Rain , Sin Nombre virus , Temperature
13.
Article in English | MEDLINE | ID: mdl-31731686

ABSTRACT

Twenty-three water dams located in the Iberian Pyrite Belt were studied during March 2012 (early spring) in order to carry out an environmental assessment based on diatom communities and to define the relationships between these biological communities and the physico-chemical characteristics of the dam surface water. This is the first time that a diatom inventory has been done for dams affected by acid mine drainage (AMD) in the Spanish part of the Iberian Pyrite Belt (IPB). It was found that the pH was the main factor influencing the behaviour of the diatom communities. Then, using a dbRDA approach it was possible to organize the aggrupation of diatoms into four groups in response to the physico-chemical conditions of the ecosystem, especially pH: (1) Maris, Aac, Gos, Cmora (pH 2-3); (2) Andc, San, And, Dpin (pH 3-4.5); (3) Gran, Pleon, Oliv, Lagu, Chan, SilI, SilII, Joya, Gar, Agrio, Camp, Corum (pH 4.5-6); (4) Herr, Diq I, Diq II (pH 6-7). The obtained results confirmed the response of benthic diatom communities to changes in the physico-chemical characteristics of surface water, and helped to understand the role of diatoms as indicators of the degree of AMD contamination in those 23 dams. Special attention was given to those that have an acidophilic or acid-tolerant profile (pH 2-3 and pH 3-4.5) such as Pinnularia aljustrelica, Pinnularia acidophila, Pinnularia acoricola and Eunotia exigua, which are the two groups found in the most AMD contaminated dams.


Subject(s)
Acids/analysis , Diatoms/growth & development , Mining , Rivers/chemistry , Rivers/microbiology , Water Pollutants, Chemical/analysis , Ecosystem , Environmental Monitoring/methods , Hydrogen-Ion Concentration , Iron/chemistry , Seasons , Spain , Sulfides/chemistry
14.
Nutrients ; 11(11)2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31683850

ABSTRACT

To determine whether elevated intra-abdominal pressure (IAP) is associated with a higher rate of enteral nutrition-related gastrointestinal (GI) complications; to assess the value of IAP as a predictor of enteral nutrition (EN) intolerance. Intensive Care Unit (ICU) patients on mechanical ventilation requiring at least 5 days of EN were recruited for a prospective, observational, non-interventional, multicenter study. EN was performed and GI complications were managed with an established protocol. IAP was determined via a urinary catheter. Patients who developed any GI complications were considered as presenting EN intolerance. Variables related to EN, IAP and GI complications were monitored daily. Statistical analysis compared patients without GI complications (group A) vs. GI complications (group B). 247 patients were recruited from 28 participating ICUs (group A: 119, group B: 128). No differences between groups were recorded. Patients in group B (p < 0.001) spent more days on EN (8.1 ± 8.4 vs. 18.1 ± 13.7), on mechanical ventilation (8.0 ± 7.7 vs. 19.3 ± 14.9) and in the ICU (12.3 ± 11.4 vs. 24.8 ± 17.5). IAP prior to the GI complication was (14.3 ± 3.1 vs. 15.8 ± 4.8) (p < 0.003). The best IAP value identified for EN intolerance was 14 mmHg but it had low sensitivity and specificity. Although a higher IAP was associated with EN intolerance, IAP alone did not emerge as a good predictor of EN intolerance in critically ill patients.


Subject(s)
Abdomen , Critical Illness/therapy , Enteral Nutrition/adverse effects , Gastrointestinal Diseases/etiology , Pressure , Aged , Biomarkers , Critical Care , Female , Humans , Intensive Care Units , Male , Middle Aged , Prospective Studies , Respiration, Artificial
15.
J Clin Med ; 8(11)2019 Nov 02.
Article in English | MEDLINE | ID: mdl-31684004

ABSTRACT

Atrial fibrillation (AF) is a sustained cardiac arrhythmia associated with stroke, heart failure, and related health conditions. Though easily diagnosed upon presentation in a clinical setting, the transient and/or intermittent emergence of AF episodes present diagnostic and clinical monitoring challenges that would ideally be met with automated ambulatory monitoring and detection. Current approaches to address these needs, commonly available both in smartphone applications and dedicated technologies, combine electrocardiogram (ECG) sensors with predictive algorithms to detect AF. These methods typically require extensive preprocessing, preliminary signal analysis, and the integration of a wide and complex array of features for the detection of AF events, and are consequently vulnerable to over-fitting. In this paper, we introduce the application of symbolic recurrence quantification analysis (SRQA) for the study of ECG signals and detection of AF events, which requires minimal pre-processing and allows the construction of highly accurate predictive algorithms from relatively few features. In addition, this approach is robust against commonly-encountered signal processing challenges that are expected in ambulatory monitoring contexts, including noisy and non-stationary data. We demonstrate the application of this method to yield a highly accurate predictive algorithm, which at optimal threshold values is 97.9% sensitive, 97.6% specific, and 97.7% accurate in classifying AF signals. To confirm the robust generalizability of this approach, we further evaluated its performance in the implementation of a 10-fold cross-validation paradigm, yielding 97.4% accuracy. In sum, these findings emphasize the robust utility of SRQA for the analysis of ECG signals and detection of AF. To the best of our knowledge, the proposed model is the first to incorporate symbolic analysis for AF beat detection.

16.
Front Immunol ; 10: 1340, 2019.
Article in English | MEDLINE | ID: mdl-31281311

ABSTRACT

Ofatumumab is the first, fully human, anti-CD20 monoclonal antibody in Phase 3 development for multiple sclerosis (MS). The study focused on changes in lymphocyte subsets in blood and lymphoid tissues and on potential novel biomarkers as a result of anti-CD20 antibody action in Cynomolgus monkeys treated with human equivalent doses of subcutaneous (s.c.) ofatumumab on Days 0, 7, and 14. Axillary lymph nodes (LNs) and blood samples were collected at various time points until Day 90. Lymphocyte subsets were quantified by flow cytometry, while morphological and immune cell changes were assessed by imaging mass cytometry (IMC), immunohistochemistry (IHC), in situ hybridization (ISH), and transcriptome analyses using single-cell methodology. Ofatumumab treatment resulted in a potent and rapid reduction of B cells along with a simultaneous drop in CD20+ T cell counts. At Day 21, IHC revealed B-cell depletion in the perifollicular and interfollicular area of axillary LNs, while only the core of the germinal center was depleted of CD20+CD21+ cells. By Day 62, the perifollicular and interfollicular areas were abundantly infiltrated by CD21+ B cells and this distribution returned to the baseline cytoarchitecture by Day 90. By IMC CD20+CD3+CD8+ cells could be identified at the margin of the follicles, with a similar pattern of distribution at Day 21 and 90. Single-cell transcriptomics analysis showed that ofatumumab induced reversible changes in t-distributed stochastic neighbor embedding (t-SNE) defined B-cell subsets that may serve as biomarkers for drug action. In summary, low dose s.c. ofatumumab potently depletes both B cells and CD20+ T cells but apparently spares marginal zone (MZ) B cells in the spleen and LN. These findings add to our molecular and tissue-architectural understanding of ofatumumab treatment effects on B-cell subsets.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , B-Lymphocytes , Genomics , Lymph Nodes , Lymphocyte Depletion , Mass Spectrometry , Single-Cell Analysis , Animals , B-Lymphocytes/cytology , B-Lymphocytes/immunology , Gene Expression Profiling , In Situ Hybridization , Lymph Nodes/cytology , Lymph Nodes/immunology , Macaca fascicularis
17.
Ultrason Sonochem ; 40(Pt B): 3-8, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28438402

ABSTRACT

This paper reports that ultrasonic (US) and hydrodynamic cavitation (HC) are efficient strategies for the environmental remediation of cork wastewater (CW). It is necessary to remove toxic, inhibitory or refractory organic matter from CW using physical and chemical techniques (pre-treatment) prior to performing conventional biological treatment. After this biological treatment, it is also critical to further decontaminate (post-treatment) in order to meet the discharge limitation. The pre-treatment of diluted CW using Fenton oxidation (FE) alone led to COD and polyphenol (PP) removal values of 30% and 61%, respectively, while HC and US resulted in 83-90% increases in COD reduction and 26-33% increases in PP reduction. Whereas 55% and 91% COD and PP removal were achieved using flocculation (Floc) alone, COD elimination was increased by a further 7-18% under HC and US. No noticeable improvement in PP elimination was observed. US did not enhance the Floc decontamination of the original concentrated CW, however, considerable quantities of white biofilm were surprisingly generated on the CW surface after the pre-treatment, thus indicating the improvement of biodegradability of the resulting liquid. In fact, the post-treatment stage, using FE alone after having filtered the biofilms, led to reductions of 53% in COD and 90% in PP. The HC and US protocols resulted in 26-34% increases in COD elimination. HC further enhanced PP elimination caused by FE, while US resulted in lower levels of PP elimination.

19.
Neuron ; 89(1): 177-93, 2016 Jan 06.
Article in English | MEDLINE | ID: mdl-26711119

ABSTRACT

Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease.


Subject(s)
Amacrine Cells/cytology , Cytoskeletal Proteins/metabolism , Nerve Net/physiology , Neural Inhibition/physiology , Nystagmus, Congenital/metabolism , Visual Pathways/physiology , Action Potentials/physiology , Animals , Mice, Transgenic , Motion Perception/physiology , Photic Stimulation/methods , Retina/physiology , Retinal Ganglion Cells/cytology , Synapses/metabolism
20.
Environ Sci Pollut Res Int ; 23(4): 3256-66, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26490895

ABSTRACT

Cu, Pb, and As, which are among the most abundant metals in the aquatic environment, are also among the most health-threatened by causing diverse cellular injuries. The aim of this study was to assess and compare the potential early induction of genotoxic effects after waterborne Cu, Pb, and As exposure in European seabass, Dicentrarchus labrax, a commercial widely cultured fish, using the micronucleus (MN) assay in peripheral blood erythrocytes. Fish were exposed under laboratory conditions to nominal solutions ranging 0-10 mg/L for 24 and 96 h. Furthermore, actual metal ion concentrations were measured by inductively coupled plasma atomic emission spectroscopy (ICP-AES) or differential pulse anodic stripping voltammetry (DPASV) in water and four fish tissues differentially related to environmental exposition and metal accumulation, i.e. the gills, liver, muscle, and brain. Dose-dependent increases of micronuclei (MNi) frequency were observed after these very short exposures; based on measured metal concentrations in water, the genotoxic effect ordered as Cu > As > Pb. Significant genotoxic effect at 0.009 mg/L Cu, 0.57 mg/L Pb, and 0.01 mg/L As was seen. For Cu and Pb these are only slightly higher, but for As it is notably lower than the USEPA criteria of maximum concentration to prevent acute toxicity in aquatic organisms. Furthermore, genotoxicity was differentially related to metal accumulation. MNi frequency correlated positively with the content of Pb in all the organs, with the content of As in liver and gills and only with the content of Cu in the brain. In conclusion, our findings raised environmental concerns because these depicted a genotoxic potential of Cu, Pb, and As after a very short exposure to low but environmentally relevant concentrations, too close to regulatory thresholds. In addition, the MN test in D. labrax could be considered an early biomarker of genotoxicity induced by these metals in fish.


Subject(s)
Arsenic/toxicity , Bass , Copper/toxicity , Lead/toxicity , Mutagens/toxicity , Water Pollutants, Chemical/toxicity , Animals , Arsenic/analysis , Copper/analysis , DNA Damage , Micronucleus Tests , Spectrophotometry, Atomic , Water Pollutants, Chemical/analysis
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