Prediction of bioavailability and toxicity of complex chemical mixtures through machine learning models.

Empirical data from a 6-month mesocosms experiment were used to assess the ability and performance of two machine learning (ML) models, including artificial neural network (NN) and random forest (RF), to predict temporal bioavailability changes of complex chemical mixtures in contaminated soils amended with compost or biochar. From the predicted bioavailability data, toxicity response for relevant ecological receptors was then forecasted to establish environmental risk implications and determine acceptable end-point remediation. The dataset corresponds to replicate samples collected over 180 days and analysed for total and bioavailable petroleum hydrocarbons and heavy metals/metalloids content. Further to this, a range of biological indicators including bacteria count, soil respiration, microbial community fingerprint, seeds germination, earthworm's lethality, and bioluminescent bacteria were evaluated to inform the environmental risk assessment. Parameters such as soil type, amendment (biochar and compost), initial concentration of individual compounds, and incubation time were used as inputs of the ML models. The relative importance of the input variables was also analysed to better understand the drivers of temporal changes in bioavailability and toxicity. It showed that toxicity changes can be driven by multiple factors (combined effects), which may not be accounted for in classical linear regression analysis (correlation). The use of ML models could improve our understanding of rate-limiting processes affecting the freely available fraction (bioavailable) of contaminants in soil, therefore contributing to mitigate potential risks and to inform appropriate response and recovery methods.

Specific immunotherapy in local allergic rhinitis: A randomized, double-blind placebo-controlled trial with Phleum pratense subcutaneous allergen immunotherapy.

BACKGROUND: Allergen immunotherapy has been shown to be an effective treatment for local allergic rhinitis (LAR) to house dust mites. Studies with pollen allergen immunotherapy are limited to observational studies. The aim of this study was to evaluate the clinical efficacy and safety of Phleum pratense subcutaneous immunotherapy (Phl-SCIT) in LAR. METHODS: In a randomized double-blind placebo-controlled study, 56 patients with moderate-severe LAR to grass pollen received Phl-SCIT with a depigmented polymerized pollen vaccine or placebo for the first year, and Phl-SCIT the second one. The blind was maintained throughout the study. Primary outcome was combined symptom medication score (CSMS) during grass pollen season (GPS). Secondary clinical outcomes included organ-specific symptoms, medication-free days, rhinitis severity and asthma control. Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), nasal allergen provocation test (NAPT), skin testing, serum levels of specific IgG4 and specific IgE and safety were also evaluated. RESULTS: Subcutaneous immunotherapy (SCIT) had a short-term and sustained effect with significant improvements of all primary and secondary clinical outcomes and RQLQ score. SCIT significantly increased serum sIgG4 levels and allergen tolerance, from the 6th to 24th months of treatment. At the end of the study, 83% of patients treated with ≥6 months of SCIT tolerated a concentration of P. pratense over 50 times higher than baseline, and 56% gave a negative NAPT. SCIT was well tolerated; six mild local reactions occurred, and there were no serious adverse events related to the study medication. CONCLUSIONS: Subcutaneous immunotherapy with depigmented polymerized allergen extracts is a safe and clinically effective treatment for LAR to P. pratense.

Seasonal Local Allergic Rhinitis in Areas With High Concentrations of Grass Pollen.

BACKGROUND: Local allergic rhinitis (LAR) is a phenotype of allergic rhinitis characterized by the presence of a localized immune response in the nasal mucosa of patients with negative skin prick test (SPT) results and undetectable serum specific IgE (sIgE). It unknown whether LAR is limited to areas with low or moderate aeroallergen exposure. OBJECTIVE: To explore the presence of LAR and the clinical and immunological characteristics of this entity in geographic areas with high grass pollen loads. METHODS: A cross-sectional observational study was carried out in 2 hospitals in central Spain (Madrid and Ciudad Real). Sixty-one patients with seasonal rhinitis and negative SPT results and undetectable serum sIgE were evaluated using a clinical questionnaire, determination of serum total IgE, and a nasal allergen provocation test (NAPT) with Phleum species. The response to NAPT was monitored using assessment of nasal symptoms, acoustic rhinometry, and determination of sIgE, tryptase, and eosinophil cationic protein in the nasal cavity. RESULTS: Seasonal LAR was detected in 37 patients (61%) using the techniques described above. Eleven percent of patients with LAR were adolescents or children, and 14% reported onset of rhinitis in childhood. Most patients reported persistent-moderate seasonal nasal symptoms, and 41% reported worsening of the disease during the last 2 years. Conjunctivitis was the most common comorbidity, affecting 95% of cases. CONCLUSIONS: LAR to grass pollen is relevant in patients with seasonal symptoms indicative of allergic rhinitis but with a negative skin test result who live in areas with high allergenic pollen loads. This entity should be included the differential diagnosis of rhinitis.

Immunologic responses to the major allergen of Olea europaea in local and systemic allergic rhinitis subjects.

OBJECTIVE: To evaluate the in vivo and in vitro responses to nOle e 1 in allergic rhinitis (AR) and local allergic rhinitis (LAR) patients sensitized to olive tree pollen (OL) confirmed by nasal allergen provocation test (NAPT). METHODS: Twelve subjects with AR, 12 with LAR and 12 subjects as control group (CG) were selected. Skin testing and NAPT with nOle e 1 were performed. Eosinophilic cationic protein (ECP) and tryptase were measured in nasal lavages before and after NAPT. Serum IgE to OL allergens was measured by ELISA. Basophil activation tests (BAT) with OL and nOle e 1 and dendritic cell maturation/proliferation studies were carried out. RESULTS: All AR (12/12) and 10/12 (83%) of LAR had a +NAPT to nOle e 1. ECP levels in nasal lavages were significantly increased after NAPT in both AR and LAR compared with CG at 15 min (P < 0.05). Serum IgE was positive only in AR. All AR had +BAT responses to OL and 10/12 to nOle e 1 (83%); 8/12 LAR (66.6%) had a +BAT to OL and 4/12 (33%) to nOle e 1, with only one subject of the CG with a +BAT to both OL and nOle e 1 (8%). Dendritic cell proliferation to nOle e 1 was increased in AR compared to LAR and CG (P = 0.019 and P = 0.001, respectively). CONCLUSION: Both AR and LAR had a similar in vivo response to nOle e 1 with release of inflammatory mediators. Specific basophil activation with OL and nOle e 1 was observed in LAR confirming previous data obtained with dust mites.

Efecto de la estimulación auditiva a una frecuencia de 5 Hz en la memoria verbal / Impact of auditory stimulation at a frequency of 5 Hz in verbal memory

Introducción. El objetivo de este estudio es establecer si la estimulación a 5 Hz favorece el recuerdo inmediato de palabras. Método. Veinte participantes recibieron estimulación auditiva a frecuencias de 5 Hz-theta, 13 Hz-beta, ruido blanco (RB) y palabras. Resultados. Los resultados indican diferencias significativas en número de palabras recordadas por día entre las frecuencias. A partir del día 3 hasta el día 5 se observó una asociación significativa entre un mayor número de palabras recordadas con 5 Hz comparadas con las demás frecuencias. Si tenemos en cuenta el número de palabras recordadas durante el registro en la magnetoencefalogrofia, en la segunda medida se encontró diferencias significativas con mayor número de palabras entre 5 Hz y 13 Hz y entre 5 Hz y RB. En la frecuencia mediana sólo se presentaron diferencias significativas en estimulación a una frecuencia de 5 Hz. Conclusión. La estimulación auditiva durante largo tiempo a una frecuencia de 5 Hz genera un acoplamiento de la actividad cerebral a dicho ritmo que aumenta la capacidad de memoria verbal inmediata (AU)

Introduction. The objective of this study was to establish whether stimulation at 5 Hz enables immediate words recall. Method. A total of 20 participants received auditory stimulation at 5 Hz-theta, beta-13 Hz frequencies, white noise (WN) and words. Results. The results indicate significant differences in the number of recalled words per day depending on the stimulation frequencies. From the third to the fifth day a significant association was shown between increasing numbers of recalled words at 5 Hz compared with the rest of the frequencies. If we take the number of words recorded during the recording of the magnetoencephalography into account, significant differences with greater numbers of words between 5 Hz and between13 Hz and 5 Hz and WN were found in the second measure. The median frequency only showed significant differences in stimulation at a frequency of 5 Hz. Conclusion. Auditory stimulation over a long time at a frequency of 5 Hz generates a coupling of brain activity that increases the capacity of immediate verbal memory (AU)

Impact of auditory stimulation at a frequency of 5 Hz in verbal memory.

INTRODUCTION: The objective of this study was to establish whether stimulation at 5 Hz enables immediate words recall. METHOD: A total of 20 participants received auditory stimulation at 5 Hz-theta, beta-13 Hz frequencies, white noise (WN) and words. RESULTS: The results indicate significant differences in the number of recalled words per day depending on the stimulation frequencies. From the third to the fifth day a significant association was shown between increasing numbers of recalled words at 5 Hz compared with the rest of the frequencies. If we take the number of words recorded during the recording of the magnetoencephalography into account, significant differences with greater numbers of words between 5 Hz and between 13 Hz and 5 Hz and WN were found in the second measure. The median frequency only showed significant differences in stimulation at a frequency of 5 Hz. CONCLUSION: Auditory stimulation over a long time at a frequency of 5 Hz generates a coupling of brain activity that increases the capacity of immediate verbal memory.

Seasonal idiopathic rhinitis with local inflammatory response and specific IgE in absence of systemic response.

BACKGROUND: Patients with idiopathic rhinitis (IR) are considered to be nonallergic because they have a negative skin prick test (SPT) and allergen specific-IgE in serum. The concept of localized mucosal allergy in the absence of atopy has recently been proposed. The immunological mechanisms involved in seasonal IR have not been sufficiently studied. We examined nasal mucosa inflammation, the presence of nasal specific-IgE and the response to nasal allergen provocation test (NAPT) in patients with seasonal IR who presented symptoms only in spring. METHODS: We evaluated 32 patients with seasonal IR and 35 with persistent allergic rhinitis to pollen (PAR-P) and compared these with healthy controls and persons with PAR to house dust mite during the pollen season, as well as by NAPT out-of-season with grass and Olea europea. We measured the nasal leukocyte-lymphocyte phenotype (CD45, CD33, CD16, CD3, CD4 and CD8), eosinophil-cationic-protein, and total and specific-IgE to grass and olive pollen in serum and nasal lavage and performed NAPT. RESULTS: In the IR group, 62.5% had a positive NAPT (IR-PosNAPT), 20/32 to grass, with four of these having a positive NAPT to olive pollen as well. IR-PosNAPT patients showed a similar nasal leukocyte-lymphocyte profile to the PAR-P patients and different to controls. We detected nasal specific-IgE in 35% of IR-PosNAPT patients. CONCLUSIONS: These results support the hypothesis that a subgroup of patients with IR have seasonal symptoms with evidence of a nasal allergic immune reaction in the absence of a positive SPT or serum specific IgE.

Manejo de la lesión medular debida a una malformación arteriovenosa / Management of spinal cord lesions due to arteriovenous malformations

Las malformaciones arteriovenosas (MAV) medulares son una patología poco frecuente, comúnmente denominadas como enfermedades raras. Causan diferentes daños a nivel de la médula espinal, dependiendo del tipo de MAV. En este caso clínico, un varón de 34 años con parestesias y paraparesia progresiva es diagnosticado mediante una resonancia magnética nuclear de mielopatía aguda dorsal, precisando realizar una angiografía medular donde se descubrió la fístula arteriovenosa. El tratamiento de las MAV va dirigido a restablecer el flujo normal en la vascularización arteriovenosa medular mediante la embolización de la fístula por vía endovascular. El tratamiento rehabilitador va encaminado a conseguir la mínima discapacidad posible. En este caso, consistió en la potenciación de los diferentes grupos musculares mediante cinesiterapia y electroestimulación con el fin de conseguir su total independencia a la hora de realizar las actividades de la vida diaria

Arteriovenous malformations (AVM) in the spinal cord are uncommon. Depending on the type of AVM, different types of damage to the spinal cord are caused. In this clinical case, a 34-year-old man with paresthesia and progressive paraparesis was diagnosed with acute thoracic myelopathy using magnetic resonance imaging; angiography of the spinal cord revealed an arteriovenous fistula. Treatment of AVM aims to reestablish normal flow in the arteriovenous vascularization of the spinal cord by endovascular embolization of the fistula. Rehabilitation treatment is directed toward achieving the minimum disability possible. In this case, it consisted of strengthening the different muscle groups through kinesitherapy and electrostimulation in order to achieve their total independence when carrying out routine daily activities

Evidence of biochemical and biomagnetic interactions in Alzheimer's disease: an MEG and MR spectroscopy study.

BACKGROUND: Several neuroimaging studies have shown reliable differences between Alzheimer's disease (AD) patients and age-matched controls. However, few studies have demonstrated the interactions between neuroimaging methods for the diagnoses of AD. OBJECTIVE: In this study, we try to elucidate the complementary nature of magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS) examinations in the assessmentof AD. METHODS: Ten patients fulfilling the NINCDS-ADRDA criteria of probable AD, and 10 elderly individuals with no history of neurological or psychiatric illness serving as age-matched controls participated in the study. All patients and controls received an MRS, MEG and neuropsychological assessment. MEG data were obtained in the context of a working memory task, previously utilized in a similar sample of patients. RESULTS: The AD group showed a reduced number of activity sources over left temporoparietal areas during the late portion of the evoked magnetic field (between 400-800 ms), as well as a bilateral temporoparietal increase in creatine and myoinositol concentrations, and in the myoinositol/N-acetyl-aspartate ratio. The combination of the variables 'number of dipoles during the late portion of the evoked magnetic field' and 'myoinositol/N-acetyl-aspartate ratio' accounted for 65% of the variance of the Mini Mental State Examination scores. CONCLUSIONS: These results highlight the importance of assessing the complex brain pathology underlying AD by utilizing multiple brain examination modalities in a coordinate approach.

Comparison of toluene-induced and styrene-induced hearing losses.

Toluene and styrene are industrial solvents that can severely damage the auditory function in adult rats. In the present study, toluene (1000 to 2000 ppm) and styrene doses (500 to 1500 ppm) were investigated according to the same schedule: 6 hours per day, 5 days per week, for 4 consecutive weeks. The auditory function of the animals was tested by recording evoked potentials from the inferior colliculus over a frequency range from 2 to 32 kHz, whereas pathological data were evaluated by conventional histologic techniques. The permanent threshold shifts (PTS) were obtained with a styrene dose 2.4 times lower than that of the toluene. The slope of the regression line (PTS/doses) was 2.1 steeper with styrene than that obtained with toluene in the same experimental conditions. The sequence of histopathological events along the organ of Corti, especially the orderliness and the location of the traumas, was similar for paired concentrations of styrene and toluene, which were respectively 650 ppm, 1500 ppm for the first match, and 850 ppm, 1750 ppm for the second one. Both electrophysiological and histological findings point out the higher ototoxic potency of the styrene compared to that of the toluene. Assumptions concerning the ototoxic mechanism are addressed in the present paper.

Effects of noise on inferior colliculus evoked potentials and cochlear anatomy in young and aged chinchillas.

Like many aging humans, the aging chinchilla tends to lose high-frequency sensitivity at a faster rate than low-frequency sensitivity. This feature, combined with its excellent low-frequency hearing, makes the chinchilla attractive as an animal model for studying the relationship between noise-induced hearing loss (NIHL) and age-related hearing loss (AHL). In the present study, we examined susceptibility to noise in 15 aged (10-15 years old) and 15 young chinchillas. Two levels of noise were used, with the aim of determining whether age-related differences exist in the magnitude and rate of recovery from temporary threshold shifts produced by a moderate-level (95 dB) noise exposure, or in susceptibility to permanent threshold shifts and cochlear damage caused by a high-level (106 dB) noise exposure. Thresholds and response amplitudes at 0.5, 1, 2, 4, 8 and 16 kHz were determined from evoked potentials recorded from the inferior colliculus. Cochlear histology was performed on animals exposed to high-level noise. The results suggest that older animals are equally vulnerable to moderate-level noise, but may be slightly more vulnerable to high-level noise. For moderate-level exposures, there appears to be a simple additive relationship (in dB) between AHL and NIHL. For high-level exposures, the relationship may be more complex.

A strategic framework for infant mortality reduction: implications for "Healthy Start".

The high infant mortality rate in the United States, especially in urban areas, remains a major federal concern. Four strategies for reducing infant mortality in cities participating in the federal ¿Healthy Start¿ are reducing high-risk pregnancies; reducing the incidence of low birthweight and preterm births; improving birthweight-specific survival; and reducing specific causes of post-neonatal mortality. Estimates of the impact of known interventions indicate that the reduction in infant mortality would be large for only one strategy: improving birthweight-specific survival. Most interventions yield a 2 percent reduction, or less, in mortality and when combined, would amount to about 30 percent. This strategic model provides a realistic framework to assess the impact of the Healthy Start demonstration and is useful in highlighting the interventions most likely to reduce infant mortality in a population.

Anatomical effects of impact noise.

Four groups of binaural chinchillas were exposed to impact noise (B-duration = 200 ms) ranging from 119 dB to 137 dB peak equivalent SPL at repetition rates of 1/s or 4/s. The duration of exposure was adjusted so that each exposure consisted of equal acoustic energy. Animals were then sacrificed immediately, 24 h or 30 days after the exposure and their cochleas subjected to scanning electron microscopy. For exposures of 119 dB or greater, there appeared to be direct mechanical damage, including large clefts between the third row of outer hair cells and Deiters' cells and fracture of tight cell junctions at the reticular lamina. There was also a progressive increase in cochlear damage over the 30 days of recovery. The patterns of cochlear pathology are compared with hearing losses and cochleograms of chinchillas previously subjected to similar exposures and with results of studies using higher level impulse noise. The results are discussed in terms of 'critical level' for impact and impulse noise.

[Hypolactatemic effect of sodium difluoroacetate]. / Etude de l'effet hypolactatémiant du difluoroacétate de sodium.

In the anesthetized rat, the intraperitoneal injection of 40 mg/kg sodium difluoroacetate (DFA), an activator of the pyruvate dehydrogenase, counteracted the hyperlactatemia induced by a high dose of phenformin (40 mg/kg) injected concomitantly. In the normal conscious dog, the administration of 150 mg/kg by gastric intubation decreased the blood lactate and pyruvate levels; however, this effect was less marked than that produced by the same dose of sodium dichloroacetate (DCA).